Molecular Medicine Reports Molecular Medicine Reports 1791-2997 1791-3004 D.A. Spandidos 10.3892/mmr.2025.13509 MMR-31-6-13509 Review Role of DNA methylation and non‑coding RNAs expression in pathogenesis, detection, prognosis, and therapy‑resistant ovarian carcinoma (Review) Del Castillo FalconiVictor M. 1 Godinez RodriguezJenny A. 2 Fragoso-OntiverosVerónica 1 Contreras-EspinosaLaura 1 3 Pedroza-TorresAbraham 4 Díaz-ChávezJosé 1 5 HerreraLuis A. 1 5 Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico Celular Biology Department of Science Faculty, UNAM, Mexico City 04510, Mexico Biological Sciences Postgrade, UNAM, Mexico City 04510, Mexico Investigadores por México Program - SECIHTI, Hereditary Cancer Clinic, INCan, Mexico City 14080, Mexico School of Medicine and Health Sciences, Mexico-Monterrey Institute of Technology, Mexico City 14380, Mexico Correspondence to: Dr Luis A. Herrera, Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico, 22 Av. San Fernando, Mexico City 14080, Mexico, E-mail: lherrera@inmegen.gob.mx Dr José Díaz-Chavez, School of Medicine and Health Sciences, Mexico-Monterrey Institute of Technology, 222 Avenue Puente, Mexico City 14380, Mexico, E-mail: jdiazchavez03@gmail.com 06 2025 01 04 2025 31 6 144 04072024 17122024 Copyright: © 2025 Del Castillo Falconi et al. 2025 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Ovarian cancer is the deadliest gynecological cancer globally, with epithelial ovarian cancer (EOC) comprising up to 90% of cases. A molecular characterization linking the histological subtypes with tumor grade in EOC has been suggested. Variations in genetic biomarkers such as BRCA1/2, MSH2, MLH1/6, BRIP1, and RAD51C/D have been studied in EOC. In addition, molecular characteristics, including DNA methylation and RNA transcription, are being explored as potential new biomarkers for the diagnosis and prognosis of this type of neoplasia. The present review focused on the role of DNA methylation and non-coding RNA expression in the development of ovarian carcinomas and their association with diagnosis, prognosis, and the resistance of cancer cells to radiotherapy and chemotherapy. The present review considered the transition from the DNA structure to the RNA expression in ovarian carcinoma.

 ovarian carcinomas DNA methylation miRNAs lncRNAs biomarkers Programa de Posgrado en Ciencias Biológicas, UNAM Ph.D. student LCE in the Programa de Posgrado en Ciencias Biológicas National Cancer Institute, México (INCAN) and CONAHCYT supported this project CMIC: 295466 CBF 2023-2024-4004 National Cancer Institute of México. Institutional Review Board Statement This article was supported by the Programa de Posgrado en Ciencias Biológicas, UNAM. This article is part of the productivity work of the Ph.D. student LCE in the Programa de Posgrado en Ciencias Biológicas, UNAM, and received a fellowship from CONACYT Currículum Vitae Único (CVU)- 1003211. National Cancer Institute, México (INCAN) and CONAHCYT supported this project (grant nos. CMIC: 295466 and CBF 2023-2024-4004). The content is solely the authors´s responsibility and does not necessarily represent the official views of the National Cancer Institute of México. Institutional Review Board Statement. Introduction

Ovary cancer (OC) is considered the most lethal malignancy among gynecological cancers. In 2020 worldwide, OC caused 1.6% of all new cancer-related deaths (1). Epithelial ovarian cancer (EOC) is a clinical type of OC that is already diagnosed in 90% of women patients with OC; patients with this OC type are typically diagnosed in the advanced stages of the disease (75%) when cancer has disseminated to a different abdominal tissue or metastases are present. The majority of patients (>70%) with advanced-stage OC do not respond to standard therapies, resulting in a resistant, fatal disease (2). Due to this, the identification and understanding of the molecular characteristics associated with early disease progression, prediction and clinical responses are necessary to improve survival and clinical treatment in women with EOC.

In this regard, differential cancer DNA methylation, compared with the origin tissue cells, is an early event during carcinogenesis. That is, DNA methylation is composed of concomitant global unmethylated DNA and local locus-methylated DNA. Methylated DNA consists of the addition of a methyl group in the fifth carbon of cytosine residues, forming a CpG; this addition forms 5-methylcytosine. Typical examples of DNA-methylation phenotypes have been characterized in certain types of cancer, such as colorectal carcinoma, breast carcinoma and glioma (3–8). Methylated DNA molecules are more compact than unmethylated DNA molecules (3). It has been proposed that unmethylated DNA is a characteristic of cancer while methylated DNA presents only a variable consequence depending on the locus and on the specific part of the locus in cancer cells (9,10). RNA transcription is strongly influenced by DNA methylation. Methylated loci are silenced and unmethylated loci are transcriptionally activated in ovarian carcinoma tumors. The diagnosis of patients is made by transvaginal ultrasound and detection of cancer antigen (CA)-125 levels; however, the state of DNA methylation and RNA expression in the tumors has been currently associated with the diagnosis of the histological subtypes in the different types of ovarian carcinoma, the advanced stages and, importantly, the survival of the patients.

EOC is a heterogeneous carcinoma type and every EOC subtype has its natural history of development. Specifically, cell subtypes are described by histopathological and molecular characteristics of ovarian carcinoma (11–13). However, it is considered that serous ovarian carcinomas are developed as a disease continuum, from low-grade to high-grade serous ovarian carcinomas. Evidence suggests that high-grade and low-grade serous carcinomas develop independently in their natural course of progression and they have different prognoses (12,13).

At the molecular level, the prognosis of spontaneous EOC type I and type II is associated with the EOC sub-type, the age of the patient and the treatment used. Although advances in clinical treatments have increased in the past few decades, the pathology structure remains unaltered (14). Of patients diagnosed with ovarian cancer, ~50% survive five years following diagnosis, including 29% of those with metastases of ovarian carcinoma (1). In ovarian carcinomas, several factors determine survival, including primarily histological subtype, grade, stage, cytoreductive surgery and, secondarily, ethnicity (15,16).

The mortalities associated with ovarian cancer comprise 4% of all cancer-related deaths (1,14). Germinal variations are changes in DNA locus. Germinal variants of ovarian carcinomas are present in 5% of patients with ovarian carcinoma. Ovarian carcinomas are mutated in the following two ways: In germinal DNA (DNA variants of hereditary cancer origin) or in somatic DNA (DNA variants with individual spontaneous tumor cancer origin). Variants in the germ line DNA represent 24% of OC. The majority of the genetic variants are present in BRCA in hereditary breast and ovarian cancer syndrome (HBOC), whereas other DNA repair genes are present in Lynch syndrome (LS), also called hereditary non-polyposis colorectal cancer syndrome (17).

The loci mutations with higher hereditary penetrance to develop ovarian carcinoma are those of BRCA1 or BRCA2. HBOC accounts for ~80% of hereditary ovarian carcinoma and 15% of epithelial OC cases. In HBOC, 65–85% of cancers are due to genomic variants in BRCA1 and BRCA2 genes, which are considered high penetrance for OC (18). These genes encode proteins for homologous recombination to repair DNA double-strand breaks and maintain genomic stability. In addition, germinal carcinoma with BRCA1/2 mutations develops a high-grade serous ovarian carcinoma (HGSOC) subtype (15,16,19). Other loci mutations with moderate familial penetrance involve genes implicated in OC, such as BARD1, BRIP1, PALB2, RAD50, RAD51C, NBN and MRE11A; these mutations are encoded in each gene that has been involved in OC as part of the BRCA2/Fanconi anemia signaling pathway (20). Epithelial OC deficiency in DNA mismatch repair is the second most common cause of HBOC, accounting for 10–15% of this condition. The lifetime risk of developing OC with LS is ~8–12% and the mean age at presentation is ~43 years. OC-associated genes in this pathway are the following: MLH1, MSH2, MSH6 and PMS2. Specifically, BRIP1, MLH1, MSH2, MSH6, PMS2 and EPCAM are moderate penetrance genes in OC (16–19).

It is notable that each mutated locus develops different characteristics in the phenotype of tumor cells present in the patients (19–23). By contrast, EOCs developed from a somatic spontaneous origin are heterogeneous. At the cellular level, ovarian carcinoma tumors are classified into five different types: HGSOC, low-grade serous ovarian carcinoma (LGSOC), mucinous carcinoma (MC), clear cells carcinoma (CCC) and endometrioid carcinoma (EC). Recently, DNA methylation and RNA transcription have been shown to vary in a defined way to develop EOC tumors, such as hypomethylated DNA and variation in RNA expression. It is notable that germinal variation in the DNA locus of the large non-coding RNA (lncRNA) HOTAIR is a risk cause of developing ovarian carcinoma. In addition, overexpression of HOTAIR has been found in ovarian carcinomas and it has been associated with chemotherapy resistance (24).

Ovarian carcinoma, which is resistant to radiotherapy and chemotherapy is another important problem. For example, in HGSOC, the presence of the TP53 mutation and chromosome instability (CIN) are associated with resistance to radiotherapy and standard chemotherapy, which is a mix of carboplatin and taxane (25). In addition, it has been observed that DNA methylation loci induce sensitivity to therapies. By contrast, the DNA methylation loci of the nuclear RNA transcripts are associated with resistance to treatment. In this regard, it has been proposed that ovarian carcinoma cells could be sensitized to radiotherapy and chemotherapy by the addition of DNA methylation inhibitors such as decitabine (25).

 DNA methylation in the diagnoses of ovarian carcinomas

The molecular characteristics validate the natural history of ovarian carcinoma tumors and explain the association between clinical characteristics of ovarian carcinoma, such as mutations in the expression levels of DNA, RNA and proteins with patient survival. The first characterization of ovarian carcinoma is performed by quantifying transvaginal CA-125 levels using ultrasonic waves (26). Subsequently, the characterization of the macroscopic tumors in surgery is required and finally the histological characteristics have to be defined by microscopic observations. Finally, the characterization of the genotype is proposed using nuclear characteristics to improve diagnosis and prognosis, as well as to confirm the natural history of the tumors. This is due to the phenotype of the tumor cells being associated with DNA methylation. Unmethylated DNA has been associated with nuclear size, aneuploidy, carcinoma subtypes and higher proliferation of ovarian carcinoma cells (27,28) [Table I, (29–48)].

Currently, the following examples have been demonstrated that indicate the DNA methylation status of ovarian carcinomas and describe the hypomethylated nuclear locus in the tumors compared with that of ovarian epithelial cells: The global loci markers (satellite sequences and ALU repetitive sequences) and the local loci markers. The assays used to discriminate the state of methylation currently available in human tumors are the following: Sodium bisulfite DNA treatment and pyrosequencing, reverse transcription-quantitative PCR (RT-qPCR), or methylation-specific PCR. High-resolution methods to determine cell single DNA methylation are currently available, such as droplet and digital PCR (43–50).

DNA methylation and RNA expression are associated with ovarian carcinoma cells. This indicates that RNA transcription could be inhibited due to the DNA methylation status of the locus, except for certain recent paradoxical examples led by a negative correlation in other types of cancers, where intragenic methylation correlates with gene overexpression (Table II) (51,52). In contrast to these observations, RNA expression is activated in the unmethylated DNA status of the locus (9). Therefore, RNA transcription is differentially present in ovarian carcinoma. MicroRNAs (miRs) are a class of small RNA transcripts (19–22 nucleotides) that decrease gene expression via translational inhibition or degradation of target messenger RNA (mRNA). Various miRs are differentially expressed in cancer, suggesting a link between these molecules and the different expression levels of proteins in cancer tissues (53). By contrast, large non-coding RNAs (lncRNAs) function on affecting the nuclear structure and RNA transcription. It is notable that the hypermethylated DNA of RNA loci decrease the presence of miRs and MEG3 (53–55), which is a lncRNA, so that the RNA transcripts in the normal ovarian tissue, benign epithelial tumors, benign epithelial ovarian cysts, malignant ovarian carcinoma and serous ovarian carcinoma exhibit differential expression of RNA transcripts (56–59).

It remains to be determined why DNA methylation in ovarian carcinomas is heterogeneous. In 2014, the World Health Organization classification guidelines for female reproductive tumors defined the ovarian carcinoma type in cell-level characterized ovarian carcinoma subtypes HGSOC, LGSOC, CCC, MC and EC (11–13,21,60). It was proposed that at the molecular level, the natural history of ovarian carcinomas is HGSOC. A fallopian tube epithelial origin was found when DNA methylation was compared (61,62). HGSOC has locally DNA methylations in 6 loci that differentiate HGSOC from the OSE DNA methylation pattern (ARMCX1, ICAM4, LOC134466, PEG3, PYCARD and SGNE1) (41); HGSOC overexpresses miR-223, miR-551b-3p, miR-30a-5p, miR-9 and miR-30a-5p (63–70). Other studies using miR microarrays have described the different expression patterns of serous ovarian carcinoma (70) and clear cell carcinoma (CCC), specifically the SFRP1 methylated locus (41,71,72). By contrast, DNA methylation in low-grade serous ovarian carcinoma has not been reported to date compared with other ovarian carcinoma subtypes or epithelial ovarian cells. By contrast, it has been shown that endometrioid carcinoma (EC) has similarities with endometrial and ovarian carcinomas in the promoter hypermethylated locus (73–76). CCC has been characterized by the HNF1 pathway to be unmethylated, whereas the RE alpha pathway is unmethylated, similar to OSE (71). Finally, mucinous carcinomas (MUC) exhibit 81 unmethylated genes that are different from those of HGSOC. It is notable that MUC-DNA methylation is more similar to colorectal and stomach carcinoma than HGSOC, providing additional information on the MUC origins from colorectal metaplasia (12,77). Downregulation of miR-192 and miR-2215 levels is also noted in MUC (78) (Fig. 1).

In conclusion, DNA methylation is a characteristic that varies early in the development of ovarian carcinoma cells. The vestige of a methylated locus in the origin tissues of ovarian carcinomas marks a directional methylation of every ovarian carcinoma subtype. DNA methylation and RNA expression are associated. Finally, DNA methylation and RNA transcripts are associated and differentially presented by the subtype cells.

<sec> <title>DNA methylation and ncRNA expression as prognostic biomarkers of ovarian carcinomas

The following factors are associated with the prognosis of patients with ovarian carcinoma: The variations in DNA syndromes, the ethnic origin, the origin of the gynecological pathologies, the subtypes, the advanced stages of the tumors (metastasis to lymph node, or metastasis to distant tissues), the size of residual tumor following cytoreductive surgery and the resistance of cancer cells to radiotherapy and chemotherapy. It is notable that 75% of ovarian carcinomas are of HGSOC sub-type and the patient 5-year survival following diagnosis with ovarian carcinoma is ~47%. In comparison, the survival of the women diagnosed with metastasis of ovarian carcinoma is only 29% (11,15,21–23,79,80).

The RNA expression could be driven by a random accumulation or by a directional and defined development as determined by the stages of International Federation of Gynecology and Obstetrics (FIGO) (81) in every molecular ovarian carcinoma subtype. Several pieces of evidence have concluded that RNA transcripts are overexpressed and downregulated in a directional way (Tables II and III). First, this has been presented in the diagnosis biomarkers without poor prognosis. Except for the BRCA1/2 mutation and the DNA methylation locus associated with response to chemotherapy, the RNA transcripts are not related to the prognosis of the patients or the single nucleotide polymorphism in HOXA11 that protects cells from developing HGSOC (82). This suggests that biologically, hereditary mutations have a higher risk weight than DNA methylation or RNA expression, which are more sensitive to alterations of the phenotype state but not of the patient's outcome. The nuclear characteristics determined of the advanced FIGO stages of ovarian carcinoma are CIN, DNA methylated locus in genes, such as BRCA1, FANCF, RASSF1A and Wnt5A, the downregulated levels of TUBA14B and the overexpressed RNA transcripts of the following genes and lncRNAs: MGMT, OSMR, ESR1 and FOXL2 and long non-coding (lnc)BRM, HOTAIR, HOXDAS-1 and lncSOX4 and CPS1-IT1 (83–87) (Table IV).

The assays used to analyze RNAs are transcriptomics or expression analysis of single locus transcription detected by RT-qPCR (88,89). It is notable that the overexpressed and downregulated transcripts associated with tumor development classified by FIGO stages could probably result in equilibration of their levels in the nuclear structure; in addition, the variation in transcript levels within patients has to be taken into account; for example, the levels of MLK7-AS1 and TUG1 were increased 2.5- and 2.2-fold, respectively; the levels of CASC2 were diminished 0.6-fold compared with the relative expression noted in advanced stage ovarian carcinoma cells (90–98). These types of variation in the RNA expression levels are individual assessments in ovarian carcinoma subtypes derived from a population, which are defined by comparison of the expression levels of their corresponding counterparts. However, in the majority of the studies, the ovarian cancer cells are used as a point of calibration (66,67,98–162).

Patients with advanced stages have methylated loci DNA on ER-b, RUNX3, and CAMK2N1; these alterations have been associated with poor prognosis (41–43). The lncRNAs SPRY4-IT1 and HOXA11 are associated with ovarian carcinoma transformation; they are overexpressed in ovarian carcinoma compared with ovarian untransformed cells (107,108,163–184). In addition, overexpression of the miR-200 family members and MALAT1 have been associated with poor prognosis in advanced stages with a sensitivity of 88%; specifically miR-125b overexpression exhibits a sensitivity of 75.6% (108,172,181–185). In addition, miR-199a exhibits a sensitivity of 72% related to positive lymph node metastasis (154,186–189). Moreover, miR-125b overexpression exhibits a sensitivity of 72%, which is characteristic of ovarian carcinoma, associated with 67% grade, 77% positive lymph node metastasis and 89% metastasis (190). The upregulation of the expression of CPST1-IT1 is also associated with cancer, stage and lymph node metastasis with a hazard ratio of 3.257 (P=0.004) (97). This suggests a variation in the gradual overexpression during the development of ovarian carcinomas. RNA transcripts have a directional variation of expression during the development of the natural history of ovarian carcinomas, which is initiated from the tissues of origin (Fig. 2).

 The molecular-resistant ovarian carcinoma

Molecular and cellular biology allows the improved understanding of the microscopic and macroscopic observations of ovarian carcinomas. The selection of the therapeutic methods, such as surgery, radiotherapy and chemotherapy, depends on several factors, such as the carcinoma grade, FIGO stage and patient characteristics, namely age (81). Surgery is performed to obtain the tumor via cytoreduction, which involves extracting carcinoma cells from the patient. Chemotherapy is subsequently administered following cytoreduction in cases of advanced ovarian carcinoma. By contrast, radiation therapy uses high-energy particles to destroy tumor cells, either directly or indirectly, to inhibit further cell growth. Concomitantly, radiotherapy has been commonly used as a first-line treatment for ovarian carcinoma until the 1990s. It is now rarely used alone and is typically used with surgery (191). However, radiotherapy can still be beneficial in certain ways, such as reducing tumor size prior to surgery, treating areas where cancer has spread and providing palliative care (192,193). Ovarian carcinoma cells are radiosensitive at the early stages of development (194), notably in low-grade carcinoma subtypes such as EC (195).

Chemotherapy presents a challenging environment for cells, aiming to eliminate tumor cells and improve the prognosis for patients with cancer. The standard chemotherapy treatment for ovarian carcinoma combines carboplatin and paclitaxel. Chemotherapy can alter the nuclear structure, DNA methylation and RNA expression in ovarian carcinoma cells (203–205). To date, the association of methylation with the incidence of cancer in patients is not directly known. However, DNA methylation is associated with chromosomal instability of high-grade serous ovarian carcinoma. This is the most aggressive subtype of ovarian cancer. It can be inferred that by understanding the relationship between methylation and CIN, the progression of ovarian cancer can be predicted. For example, it is known that the HGSOC subtype with TP53 mutation and CIN is associated with DNA hypermethylation in patients with poorer prognosis (206–213). HGSOC is characterized by TP53 mutation and CIN and is linked to chemotherapy resistance; it is also considered to be the more resistant and heterogeneous subtype of ovarian carcinomas (214). For example, treatment with paclitaxel in specific cell line models induces overexpression of mdr1 and the lncRNAs UCA1 and long intergenic non-coding RNA linc00312 (215).

Paclitaxel is a drug that inhibits depolymerization of microtubules. It arrests cells in the G2/M phase. It also induces CIN, leading to cell death. However, certain ovarian carcinoma cells are resistant to paclitaxel. Certain miR biomarkers, such as miR-134 and miR-224-5p, are associated with EOC resistance to paclitaxel chemotherapy with 85 and 90% sensitivity, respectively (94,102). Studies in ovarian carcinoma have shown that RNA transcript levels are altered during paclitaxel treatment in ovarian cancer cells. For example, treatment of A2780, OVCAR3, SKOV3, and SW626 cells with paclitaxel induces overexpression of mdr1 (215), UCA1 and lincRNA00312.

Previous studies have shown that cisplatin increases the expression of ZEB1 and MP63 (216,217). It is notable that the use of array expression and PCR validation in the A2780 cisplatin-resistant cell line revealed that the expression levels of the following six miRs were upregulated: miR-1064, miR-300, miR-193b, miR-642 and miR-1299; however, the expression levels of the following five miRs were downregulated: miR-625, miR-20b, miRPlus-F1147, let-7c, miR-1231 and miR-542-3p (214,215,218,219). This evidence suggests that RNA transcripts are differentially expressed in chemotherapy-resistant cells compared with sensitive cells, providing a solid basis for further research. It also indicates the implications for the survival outcomes of the patients with ovarian cancer (220–225) (Fig. 3).

 Discussion and conclusions

Ovarian carcinoma is a type of cancer resulting from tissue transformation and can occur both in hereditary (20%) and sporadic (80%) forms. DNA methylations repress RNA transcription differentially in ovarian carcinoma subtypes. This suggests that DNA methylation of ovarian carcinoma subtypes is more similar to their tissue of origin with regard to their nuclear characteristics. Ovarian carcinoma presents a complex molecular landscape where DNA methylation and RNA expression play crucial roles in the disease development, progression and treatment response. DNA methylation serves as both an early event in carcinogenesis and a key regulator of gene expression, either silencing or activating RNA transcription based on the methylation status of specific loci.

The characteristics of nuclear vestiges vary in a directional range of RNA transcripts. In addition, the directional way of variation of the RNA transcripts is directed by FIGO stages observed in every carcinoma subtype. The molecular ovarian carcinoma subtypes are five and can be classified as follows: High-grade serous, low-grade serous, endometrioid, mucinous and clear cell; however, there are other subtypes to be described since they belong in the five subtypes or other similar subtypes, such as carcinosarcoma (analogous to malignant mixed Mullerian/mesodermal tumors) and malignant Brenner tumors. Other cellular subtypes are currently in discovery. This is particularly relevant in HGSOC, where distinct methylation patterns have been identified, linking them to tumor origin, subtype differentiation and patient prognosis. The heterogeneity of ovarian carcinoma is further exemplified by the differential expression of miRs and lncRNAs, which are involved in gene regulation.

The molecular prognosis of ovarian carcinoma varies. Firstly, hereditary ovarian carcinoma exhibits a greater effect than sporadic ovarian carcinoma. By contrast, the survival of each patient with spontaneous ovarian carcinoma depends on the carcinoma development and the subtype. At a molecular level, deviations in the DNA methylation and RNA transcription have been associated with metastasis stages and the development of therapy-resistant cancer cells. These findings suggest that molecular signatures, including miR and lncRNA profiles, could serve as valuable biomarkers for diagnosis, prognosis and therapeutic targeting in ovarian carcinomas. Despite the advances in the understanding of the molecular underpinnings of ovarian carcinomas, the disease prognosis for patients, notably those diagnosed with advanced-stage or metastatic disease remains poor, with survival rates being markedly lower among these groups.

Current diagnostic and therapeutic strategies are increasingly incorporating molecular data, including RNA transcriptomics and DNA methylation analysis, to improve the precision of treatment approaches. While hereditary mutations, such as those noted in BRCA1/2, confer a significant risk, epigenetic changes, notably in the later stages of the disease, are critical in shaping the tumor phenotype and response to therapy. In clinical practice, evidence leads to the hypothesis that certain genes could be used as a combination to adjust cancer treatments. However, a pair of primers may not provide a clinical solution. Therefore, practical techniques, such as PCR and sequencing, are used for validation of the next biological characterization of chromosomes. In the present review, it was hypothesized that chromosome instability, which is characterized by gain of chromosomes in cancer cells and the loss of specific chromosomes or their translocation, should be the focus of future research. For example, changes in DNA methylation of chromosomes 9 and 19 (Figs. 2 and 3) in high-grade serous ovarian carcinoma are associated with ovarian carcinoma progression and resistance to treatments.

Ultimately, a comprehensive understanding of the molecular heterogeneity in ovarian carcinoma, including the roles of DNA methylation and RNA transcription into the nucleus, is essential to develop a vision for more effective treatments, increase the understanding of disease progression and improve long-term outcomes for patients. The continued exploration of these molecular pathways holds the potential not only to revolutionize but also to reform the clinical management of ovarian carcinomas.

 Acknowledgements

This article is part of the productivity of LCE as a PhD student of Biological Sciences Postgrade Program, in the Biomedicine Field.

 Availability of data and materials

Not applicable.

 Authors' contributions

Conceptualization and original draft preparation: VMDCF, VFO, JDC, LAH and LCE. Writing and revising the manuscript JAGR, APT, VFO, LAH and VMDCF. Supervision, project administration and funding acquisition: JDC and LAH. All authors have read and approved the final version of the manuscript. Data authentication is not applicable.

 Ethics approval and consent to participate

Not applicable

 Patient consent for publication

Not applicable.

 Competing interests

The authors declare that they have no competing interests.

 References MomenimovahedZTiznobaikATaheriSSalehiniyaHOvarian cancer in the world: epidemiology and risk factorsInt J Womens Health11287299201910.2147/IJWH.S19760431118829 SiegelRLMillerKDJemalACancer Statistics, 2016CA Cancer J Clin66730201610.3322/caac.2133226742998 LuoYHuangJTangYLuoXGeLShengXSunXChenYZhuDRegional methylome profiling reveals dynamic epigenetic heterogeneity and convergent hypomethylation of stem cell quiescence-associated genes in breast cancer following neoadjuvant chemotherapyCell Biosci916201910.1186/s13578-019-0278-y30774927 SandhuRRollJDRivenbarkAGColemanWBDysregulation of the Epigenome in Human Breast Cancer': Contributions of gene-specific DNA hypermethylation to breast cancer pathobiology and targeting the breast cancer methylome for improved therapyAm J Pathol185282292201510.1016/j.ajpath.2014.12.00325541331 MaireCLFuhMMKaulichKFitaKDStevicIHeilandDHWelshJAJonesJCGörgensARicklefsTGenome-wide methylation profiling of glioblastoma cell-derived extracellular vesicle DNA allows tumor classificationNeuro Oncol2310871099202110.1093/neuonc/noab01233508126 WangZCuiYWangFXuLYanYTongXYanHDNA methylation-regulated LINC02587 inhibits ferroptosis and promotes the progression of glioma cells through the CoQ-FSP1 pathwayBMC Cancer23989202310.1186/s12885-023-11502-037848823 WielandtAMVillarroelCHurtadoCSimianDZamoranoDMartínezMCastroMVialMTKronbergULópez-KostnerFCharacterization of patients with sporadic colorectal cancer following the new Consensus Molecular Subtypes (CMS)Rev Méd Chile1454194302017(In Spanish)10.4067/S0034-9887201700040000128748988 Moreno-OrtizJMJiménez-GarcíaJGutiérrez-AnguloMAyala-MadrigalMDGonzález-MercadoAGonzález-VillaseñorCOFlores-LópezBAAlvizo-RodríguezCHernández-SandovalJAFernández-GalindoMAHigh frequency of MLH1 promoter methylation mediated by gender and age in colorectal tumors from Mexican patientsGMM1576386442021(In Spanish) Del Castillo FalconiVMTorres-ArcigaKMatus-OrtegaGDíaz-ChávezJHerreraLADNA methyltransferases: From evolution to clinical applicationsInt J Mol Sci238994202210.3390/ijms2316899436012258 LiEBestorTHJaenischRTargeted mutation of the DNA methyltransferase gene results in embryonic lethalityCell69915926199210.1016/0092-8674(92)90611-F1606615 ShihIeMKurmanRJOvarian tumorigenesis: A proposed model based on morphological and molecular genetic analysisAm J Pathol16415111518200410.1016/S0002-9440(10)63708-X15111296 KurmanRJShihIeMPathogenesis of ovarian cancer: Lessons from morphology and molecular biology and their clinical implicationsInt J Gynecol Pathol27151160201818317228 KurmanRJShihIeMThe origin and pathogenesis of epithelial ovarian cancer: A proposed unifying theoryAm J Surg Pathol34433443201010.1097/PAS.0b013e3181cf3d7920154587 SamuelDDiaz-BarbeAPintoASchlumbrechtMGeorgeSHereditary ovarian carcinoma: Cancer pathogenesis looking beyond BRCA1 and BRCA2Cells11539202210.3390/cells1103053935159349 RamusSJHarringtonPAPyeCDiCioccioRACoxMJGarlinghouse-JonesKOakley-GirvanIJacobsIJHardyRMWhittemoreASContribution of BRCA1 and BRCA2 mutations to inherited ovarian cancerHum Mutat2812071215200710.1002/humu.2059917688236 MenonUKarpinskyjCGentry-MaharajAOvarian cancer prevention and screeningObstet Gynecol131909927201810.1097/AOG.000000000000258029630008 LavoroAScalisiACandidoSZanghìGNRizzoRGattusoGCarusoGLibraMFalzoneLIdentification of the most common BRCA alterations through analysis of germline mutation databases: Is droplet digital PCR an additional strategy for the assessment of such alterations in breast and ovarian cancer families?Int J Oncol6058202210.3892/ijo.2022.534935383859 KansuttiviwatCLertwilaiwittayaPRoothumnongENakthongPDungortPMeesamarnpongCTansa-NgaWPongsuktavornKWiboonthanasarnSTititumjariyaWGermline mutations of 4567 patients with hereditary breast-ovarian cancer spectrum in ThailandNPJ Genom Med99202410.1038/s41525-024-00400-438355628 AndrikopoulouAZografosEApostolidouKKyriazoglouAPapatheodoridiAMKaparelouMKoutsoukosKLiontosMDimopoulosMAZagouriFGermline and somatic variants in ovarian carcinoma: A next-generation sequencing (NGS) analysisFront Oncol121030786202210.3389/fonc.2022.103078636531003 GhoseABolinaAMahajanIRazaSAClarkeMPalASanchezERallisKSBoussiosSHereditary ovarian cancer: Towards a cost-effective prevention strategyInt J Environ Res Public Health1912057202210.3390/ijerph19191205736231355 McCluggageWGMorphological subtypes of ovarian carcinoma: A review with emphasis on new developments and pathogenesisPathology43420432201110.1097/PAT.0b013e328348a6e721716157 AndrewsLMutchDGHereditary ovarian cancer and risk reductionBest Pract Res Clin Obstet Gynaecol413148201710.1016/j.bpobgyn.2016.10.01728254144 LynchHTLynchJFHereditary nonpolyposis colorectal cancerSemin Surg Oncol18305313200010.1002/(SICI)1098-2388(200006)18:4<305::AID-SSU5>3.0.CO;2-A10805952 WuHShangXShiYYangZZhaoJYangMLiYXuSGenetic variants of lncRNA HOTAIR and risk of epithelial ovarian cancer among Chinese womenOncotarget74104741052201610.18632/oncotarget.853527166268 BronderDTigheAWangsaDZongDMeyerTJWardenaarRMinshallPHirschDHeselmeyer-HaddadKNelsonLTP53 loss initiates chromosomal instability in fallopian tube epithelial cellsDis Model Mech14dmm049001202110.1242/dmm.04900134569598 GoffBAMandelLMuntzHGMelanconCHOvarian carcinoma diagnosisCancer8920682075200010.1002/1097-0142(20001115)89:10<2068::AID-CNCR6>3.0.CO;2-Z11066047 ZeimetAGFieglHGoebelGKoppFAllasiaCReimerDSteppanIMueller-HolznerEEhrlichMMarthCDNA ploidy, nuclear size, proliferation index and DNA-hypomethylation in ovarian cancerGynecol Oncol1212431201110.1016/j.ygyno.2010.12.33221251700 WidschwendterMJiangGWoodsCMüllerHMFieglHGoebelGMarthCMüller-HolznerEZeimetAGLairdPWEhrlichMDNA hypomethylation and ovarian cancer biologyCancer Res6444724480200410.1158/0008-5472.CAN-04-023815231656 FengWMarquezRTLuZLiuJLuKHIssaJPFishmanDMYuYBastRCJrImprinted tumor suppressor genesARHI andPEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylationCancer11214891502200810.1002/cncr.2332318286529 LinkPAZhangWOdunsiKKarpfARBORIS/CTCFL mRNA isoform expression and epigenetic regulation in epithelial ovarian cancerCancer Immun136201323390377 WangYQYanQZhangJRLiSDYangYXWanXPEpigenetic inactivation of BRCA1 through promoter hypermethylation in ovarian cancer progressionJ Obstet Gynaecol Res39549554201310.1111/j.1447-0756.2012.01979.x23006047 Abou-ZeidAAAzzamAZKamelNAMethylation status of the gene promoter of cyclin-dependent kinase inhibitor 2A (CDKN2A) in ovarian cancerScand J Clin Lab Invest71542547201110.3109/00365513.2011.59022421728901 BhagatRKumarSSVaderhobliSPremalataCSPallaviVRRameshGKrishnamoorthyLEpigenetic alteration of p16 and retinoic acid receptor beta genes in the development of epithelial ovarian carcinomaTumour Biol3590699078201410.1007/s13277-014-2136-124913706 YangGZhangHLiuYZhouJHeWQuickCMXieDSmollerBRFanCYEpigenetic and immunohistochemical characterization of the Clusterin gene in ovarian tumorsArch Gynecol Obstet287989995201310.1007/s00404-012-2650-623208459 ZhangWBargerCJLinkPAMhawech-FaucegliaPMillerAAkersSNOdunsiKKarpfARDNA hypomethylation-mediated activation of Cancer/Testis Antigen 45 (CT45) genes is associated with disease progression and reduced survival in epithelial ovarian cancerEpigenetics10736748201510.1080/15592294.2015.106220626098711 WangBYuLLuoXHuangLLiQSShaoXSLiuYFanYYangGZDetection of OPCML methylation, a possible epigenetic marker, from free serum circulating DNA to improve the diagnosis of early-stage ovarian epithelial cancerOncol Lett14217223201710.3892/ol.2017.611128693156 KaurMSinghASinghKGuptaSSachanMDevelopment of a multiplex MethyLight assay for the detection of DAPK1 and SOX1 methylation in epithelial ovarian cancer in a north Indian populationGenes Genet Syst91175181201610.1266/ggs.15-0005127452040 RattanapanYKorkiatsakulVKongruangAChareonsirisuthigulTRerkamnuaychokeBWongkularbAWilailakSEGFL7 and RASSF1 promoter hypermethylation in epithelial ovarian cancerCancer Genet2242253740201829778234 da Conceição BragaCSilvaLMPiedadeJBTraimanPda Silva FilhoALEpigenetic and expression analysis of TRAIL-R2 and BCL2: On the TRAIL to knowledge of apoptosis in ovarian tumorsArch Gynecol Obstet28910611069201410.1007/s00404-013-3060-024190693 BonitoNABorleyJWilhelm-BenartziCSGhaem-MaghamiSBrownREpigenetic regulation of the homeobox gene MSX1 associates with platinum-resistant disease in high-grade serous epithelial ovarian cancerClin Cancer Res2230973104201610.1158/1078-0432.CCR-15-166926763252 KardumVKarinVGliboMSkrticAMarticTNIbisevicNSkenderiFVranicSSermanLMethylation-associated silencing of SFRP1 gene in high-grade serous ovarian carcinomasAnn Diagn Pathol314549201710.1016/j.anndiagpath.2017.07.00229146058 SuzukiFAkahiraJMiuraISuzukiTItoKHayashiSSasanoHYaegashiNLoss of estrogen receptor beta isoform expression and its correlation with aberrant DNA methylation of the 5′-untranslated region in human epithelial ovarian carcinomaCancer Sci9923652372200810.1111/j.1349-7006.2008.00988.x19032364 BaranovaIKovarikovaHLacoJDvorakOSedlakovaIPalickaVChmelarovaMAberrant methylation of PCDH17 gene in high-grade serous ovarian carcinomaCancer Biomark23125133201810.3233/CBM-18149329991130 DingJJWangGShiWXZhouHHZhaoEFPromoter hypermethylation of FANCF and susceptibility and prognosis of epithelial ovarian cancerReprod Sci232430201610.1177/193371911561213626507869 GozziGChelbiSTManniPAlbertiLFondaSSaponaroSFabbianiLRivasiFBenhattarJLosiLPromoter methylation and downregulated expression of the TBX15 gene in ovarian carcinomaOncol Lett1228112819201610.3892/ol.2016.501927698863 ChoiYLKangSYShinYKChoiJSKimSHLeeSJBaeDSAhnGAberrant hypermethylation of RASSF1A promoter in ovarian borderline tumors and carcinomasVirchows Archiv448331336200610.1007/s00428-005-0091-316315018 HäfnerNSteinbachDJansenLDiebolderHDürstMRunnebaumIBRUNX3 and CAMK2N1 hypermethylation as prognostic marker for epithelial ovarian cancerInt J Cancer138217228201610.1002/ijc.2969026175272 JinPSongYYuGThe role of abnormal methylation of Wnt5a gene promoter regions in human epithelial ovarian cancer: A clinical and experimental studyAnal Cell Pathol (Amst)20186567081201830079293 KhodadadiEFahmidehLKhodadadiEDaoSYousefiMTaghizadehSAsgharzadehMYousefiBKafilHSCurrent advances in DNA methylation analysis methodsBiomed Res Int20218827516202110.1155/2021/882751633824878 GattusoGLavoroACaltabianoRMadonnaGCaponeMAsciertoPAFalzoneLLibraMCandidoSMethylation-sensitive restriction enzyme-droplet digital PCR assay for the one-step highly sensitive analysis of DNA methylation hotspotsInt J Mol Med5342202410.3892/ijmm.2024.536638488030 FalzoneLSalemiRTravaliSScalisiAMcCubreyJACandidoSLibraMMMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanomaAging (Albany NY)8933944201610.18632/aging.10095127115178 SingerMKostiIPachterLMandel-GutfreundYA diverse epigenetic landscape at human exons with implication for expressionNucleic Acids Res4334983508201510.1093/nar/gkv15325765649 DavidsonBTropéCGReichRThe clinical and diagnostic role of microRNAs in ovarian carcinomaGynecol Oncol133640646201410.1016/j.ygyno.2014.03.57524713546 ShengXLiJYangLChenZZhaoQTanLZhouYLiJPromoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancerOncol Rep32277285201410.3892/or.2014.320824859196 LoginovVIProninaIVBurdennyyAMFilippovaEAKazubskayaTPKushlinskyDNUtkinDOKhodyrevDSKushlinskiiNEDmitrievAABragaEANovel miRNA genes deregulated by aberrant methylation in ovarian carcinoma are involved in metastasisGene6622836201810.1016/j.gene.2018.04.00529631007 Filippov-LevyNCohen-SchussheimHTropéCGHetland FalkenthalTESmithYDavidsonBReichRExpression and clinical role of long non-coding RNA in high-grade serous carcinomaGynecol Oncol148559566201810.1016/j.ygyno.2018.01.00429310950 LiuXDaiCJiaGXuSFuZXuJLiQRuanHXuPMicroarray analysis reveals differentially expressed lncRNAs in benign epithelial ovarian cysts and normal ovariesOncol Rep38799808201710.3892/or.2017.574128656240 LuYMWangYLiuSQZhouMYGuoYRProfile and validation of dysregulated long non-coding RNAs and mRNAs in ovarian cancerOncol Rep4029642976201830132558 WangHFuZDaiCCaoJLiuXXuJLvMGuYZhangJHuaXLncRNAs expression profiling in normal ovary, benign ovarian cyst and malignant epithelial ovarian cancerSci Rep638983201610.1038/srep3898327941916 BoydCMcCluggageWGLow-grade ovarian serous neoplasms (low-grade serous carcinoma and serous borderline tumor) associated with high-grade serous carcinoma or undifferentiated carcinoma: Report of a series of cases of an unusual phenomenonAm J Surg Pathol36368375201210.1097/PAS.0b013e31823732a922082603 PisanicTRIICopeLMLinSFYenTTAthamanolapPAsakaRNakayamaKFaderANWangTHShihIMWangTLMethylomic analysis of ovarian cancers identifies tumor-specific alterations readily detectable in early precursor lesionsClin Cancer Res2465366547201810.1158/1078-0432.CCR-18-119930108103 KlinkebielDZhangWAkersSNOdunsiKKarpfARDNA Methylome analyses implicate fallopian tube epithelia as the origin for high-grade serous ovarian cancerMol Cancer Res14787794201610.1158/1541-7786.MCR-16-009727259716 GivelAMKiefferYScholer-DahirelASirvenPCardonMPelonFMagagnaIGentricGCostaABonneauCMieuletVmiR200-regulated CXCL12β promotes fibroblast heterogeneity and immunosuppression in ovarian cancersNat Commun91056201810.1038/s41467-018-03348-z29535360 WangYQiuCLuNLiuZJinCSunCBuHYuHDongolSKongBFOXD1 is targeted by miR-30a-5p and miR-200a-5p and suppresses the proliferation of human ovarian carcinoma cells by promoting p21 expression in a p53-independent mannerInt J Oncol5221302142201829620165 MaHTianTLiangSLiuXShenHXiaMLiuXZhangWWangLChenSYuLEstrogen receptor-mediated miR-486-5p regulation of OLFM4 expression in ovarian cancerOncotarget7105941605201610.18632/oncotarget.723626871282 NymoenDASlipicevicAHolthAEmilsenEHetland FalkenthalTETropéCGReichRFlørenesVADavidsonBMiR-29a is a candidate biomarker of better survival in metastatic high-grade serous carcinomaHum Pathol547481201610.1016/j.humpath.2016.03.01027063471 ArtsFAKeoghLSmythPO'TooleSTaRGleesonNO'LearyJJFlavinRSheilsOmiR-223 potentially targets SWI/SNF complex protein SMARCD1 in atypical proliferative serous tumor and high-grade ovarian serous carcinomaHum Pathol7098104201710.1016/j.humpath.2017.10.00829079174 Chaluvally-RaghavanPJeongKJPradeepSSilvaAMYuSLiuWMossTRodriguez-AguayoCZhangDRamPDirect upregulation of STAT3 by MicroRNA-551b-3p deregulates growth and metastasis of ovarian cancerCell Rep1514931504201610.1016/j.celrep.2016.04.03427160903 ZhaoHLiuSWangGWuXDingYGuoGJiangJCuiSExpression of miR-136 is associated with the primary cisplatin resistance of human epithelial ovarian cancerOncol Rep33591598201510.3892/or.2014.364025482209 KuznetsovVATangZIvshinaAVIdentification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsetsBMC Genomics18(Suppl 6)692201710.1186/s12864-017-4027-528984201 ZhangXGuoGWangGZhaoJWangBYuXDingYProfile of differentially expressed miRNAs in high-grade serous carcinoma and clear cell ovarian carcinoma, and the expression of miR-510 in ovarian carcinomaMol Med Rep1280218031201510.3892/mmr.2015.448526497752 YanaiharaNNoguchiYSaitoMTakenakaMTakakuraSYamadaKOkamotoAMicroRNA gene expression signature driven by miR-9 overexpression in ovarian clear cell carcinomaPLoS One11e0162584201610.1371/journal.pone.016258427612152 FurlanDCarnevaliIMarcominiBCeruttiRDaineseECapellaCRivaCThe high frequency of de novo promoter methylation in synchronous primary endometrial and ovarian carcinomasClin Cancer Res1233293336200610.1158/1078-0432.CCR-05-267916740754 NiskakoskiAPasanenAPorkkaNEldforsSLassusHRenkonen-SinisaloLKaurSMecklinJPBützowRPeltomäkiPConverging endometrial and ovarian tumorigenesis in Lynch syndrome: Shared origin of synchronous carcinomasGynecol Oncol1509298201810.1016/j.ygyno.2018.04.56629716739 KolbeDLDeLoiaJAPorter-GillPStrangeMPetrykowskaHMGuirguisAKrivakTCBrodyLCElnitskiLDifferential analysis of ovarian and endometrial cancers identifies a methylator phenotypePLoS One7e32941201210.1371/journal.pone.003294122403726 GuoCRenFWangDLiYLiuKLiuSChenPRUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosisOncol Rep3225802588201410.3892/or.2014.352425333219 LiewPLHuangRLWengYCFangCLHui-Ming HuangTLaiHCDistinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors: Methylation profile of MuOC and PSMB8Int J Cancer143355367201810.1002/ijc.3132429451304 AgostiniABrunettiMDavidsonBTropéCGErikssonAGZHeimSPanagopoulosIMicciFThe microRNA miR-192/215 family is upregulated in mucinous ovarian carcinomasSci Rep811069201810.1038/s41598-018-29332-730038317 VangRShihIeMKurmanRJOvarian low-grade and high-grade serous carcinoma: Pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problemsAdv Anat Pathol16267282200910.1097/PAP.0b013e3181b4fffa19700937 BowtellDDThe genesis and evolution of high-grade serous ovarian cancerNat Rev Cancer10803808201010.1038/nrc294620944665 O'SheaASClinical staging of ovarian cancerMethods Mol Biol2424310202210.1007/978-1-0716-1956-8_134918284 RichardsEJPermuth-WeyJLiYChenYACoppolaDReidBMLinHYTeerJKBerchuckABirrerMJA functional variant in HOXA11-AS, a novel long non-coding RNA, inhibits the oncogenic phenotype of epithelial ovarian cancerOncotarget63474534757201510.18632/oncotarget.578426430965 ZhangTWuDDengSHanRLiuTLiJXuYIntegrated analysis reveals that long non-coding RNA TUBA4B can be used as a prognostic biomarker in various cancersCell Physiol Biochem49530544201810.1159/00049299130157490 Meryet-FiguièreMLambertBGauduchonPVigneronNBrotinEPoulainLDenoyelleCAn overview of long non-coding RNAs in ovarian cancersOncotarget74471944734201610.18632/oncotarget.808926992233 ZhongYGaoDHeSShuaiCPengSDysregulated expression of long noncoding RNAs in ovarian cancerInt J Gynecol Cancer2615641570201610.1097/IGC.000000000000082827603915 MaYLuYLuBMicroRNA and Long Non-Coding RNA in ovarian carcinoma: Translational insights and potential clinical applicationsCancer Invest34465476201610.1080/07357907.2016.122744627673409 LinXQiuJHuaKLong non-coding RNAs as emerging regulators of epithelial to mesenchymal transition in gynecologic cancersBiosci Trends12342353201810.5582/bst.2018.0118130146551 MicheelJSafrastyanAWollnyDAdvances in non-coding RNA sequencingNoncoding RNA770202134842804 ZhangNHuGMyersTGWilliamsonPRProtocols for the analysis of microRNA expression, biogenesis, and function in immune cellsCurr Protoc Immunol126e78201910.1002/cpim.7831483103 ZhangSLengTZhangQZhaoQNieXYangLSanguinarine inhibits epithelial ovarian cancer development via regulating long non-coding RNA CASC2-EIF4A3 axis and/or inhibiting NF-κB signaling or PI3K/AKT/mTOR pathwayBiomed Pharmacother102302308201810.1016/j.biopha.2018.03.07129571014 QiuJJLinYYYeLCDingJXFengWWJinHYZhangYLiQHuaKQOverexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancerGynecol Oncol134121128201410.1016/j.ygyno.2014.03.55624662839 XiJFengJZengSLong noncoding RNA lncBRM facilitates the proliferation, migration and invasion of ovarian cancer cells via upregulation of Sox4Am J Cancer Res721802189201729218242 ZhangYDunYZhouSHuangXHLncRNA HOXD-AS1 promotes epithelial ovarian cancer cells proliferation and invasion by targeting miR-133a-3p and activating Wnt/β-catenin signaling pathwayBiomed Pharmacother9612161221201710.1016/j.biopha.2017.11.09629239819 LiuYWangYYaoDCuiDLncSOX4 serves an oncogenic role in the tumorigenesis of epithelial ovarian cancer by promoting cell proliferation and inhibiting apoptosisMol Med Rep1782828288201829693704 YanHLiHLiPLiXLinJZhuLSilvaMAWangXWangPZhangZLong noncoding RNA MLK7-AS1 promotes ovarian cancer cells progression by modulating miR-375/YAP1 axisJ Exp Clin Cancer Res37237201810.1186/s13046-018-0910-430249278 LiTChenYZhangJLiuSLncRNA TUG1 promotes cells proliferation and inhibits cells apoptosis through regulating AURKA in epithelial ovarian cancer cellsMedicine (Baltimore)97e12131201810.1097/MD.000000000001213130200102 WangYSMaLNSunJXLiuNWangHLong non-coding CPS1-IT1 is a positive prognostic factor and inhibits epithelial ovarian cancer tumorigenesisEur Rev Med Pharmacol Sci2131693175201728770969 ZhuFFZhengFYWangHOZhengJJZhangQDownregulation of lncRNA TUBA4B is associated with poor prognosis for epithelial ovarian cancerPathol Oncol Res24419425201810.1007/s12253-017-0258-728578489 YingXWeiKLinZCuiYDingJChenYXuBMicroRNA-125b suppresses ovarian cancer progression via suppression of the epithelial-mesenchymal transition pathway by targeting the SET proteinCell Physiol Biochem39501510201610.1159/00044564227383536 ZhuTGaoWChenXZhangYWuMZhangPWangSA pilot study of circulating MicroRNA-125b as a diagnostic and prognostic biomarker for epithelial ovarian cancerInt J Gynecol Cancer27310201710.1097/IGC.000000000000084627636713 TengYZhangYQuKYangXFuJChenWLiXMicroRNA-29B (mir-29b) regulates the Warburg effect in ovarian cancer by targeting AKT2 and AKT3Oncotarget64079940814201510.18632/oncotarget.569526512921 CaoQLuKDaiSHuYFanWClinicopathological and prognostic implications of the miR-200 family in patients with epithelial ovarian cancerInt J Clin Exp Pathol723922401201424966949 KapetanakisNIUzanCJimenez-PailhesASGouySBentivegnaEMoricePCaronOGourzones-DmitrievCLe TeuffGBussonPPlasma miR-200b in ovarian carcinoma patients: Distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survivalOncotarget63681536824201510.18632/oncotarget.576626416421 MengXMüllerVMilde-LangoschKTrillschFPantelKSchwarzenbachHDiagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancerOncotarget71692316935201610.18632/oncotarget.785026943577 DuZShaXDemethoxycurcumin inhibited human epithelia ovarian cancer cells' growth via up-regulating miR-551aTumour Biol391010428317694302201710.1177/101042831769430228345465 ChenSChenXXiuYLSunKXZhaoYMicroRNA-490-3P targets CDK1 and inhibits ovarian epithelial carcinoma tumorigenesis and progressionCancer Lett362122130201510.1016/j.canlet.2015.03.02925819031 ShuangTWangMShiCZhouYWangDDown-regulated expression of miR-134 contributes to paclitaxel resistance in human ovarian cancer cellsFEBS Lett58931543164201510.1016/j.febslet.2015.08.04726363097 ZouYTGaoJYWangHLWangYWangHLiPLDownregulation of microRNA-630 inhibits cell proliferation and invasion and enhances chemosensitivity in human ovarian carcinomaGenet Mol Res1487668777201510.4238/2015.July.31.2526345808 ZhangHLiWDysregulation of micro-143-3p and BALBP1 contributes to the pathogenesis of the development of ovarian carcinomaOncol Rep3636053610201610.3892/or.2016.514827748916 ZhangWZengQBanZCaoJChuTLeiDLiuCGuoWZengXEffects of let-7c on the proliferation of ovarian carcinoma cells by targeted regulation of CDC25a gene expressionOncol Lett1655435550201830405749 LiuMXSiuMKLiuSSYamJWNganHYChanDWEpigenetic silencing of microRNA-199b-5p is associated with acquired chemoresistance via activation of JAG1-Notch1 signaling in ovarian cancerOncotarget5944958201410.18632/oncotarget.145824659709 KobayashiMSawadaKNakamuraKYoshimuraAMiyamotoMShimizuAIshidaKNakatsukaEKodamaMHashimotoKExosomal miR-1290 is a potential biomarker of high-grade serous ovarian carcinoma and can discriminate patients from those with malignancies of other histological typesJ Ovarian Res1181201810.1186/s13048-018-0458-030219071 ZhaoHBiTQuZJiangJCuiSWangYExpression of miR-224-5p is associated with the original cisplatin resistance of ovarian papillary serous carcinomaOncol Rep3210031012201410.3892/or.2014.331125017423 ChenYChenQLiuQGaoFHuman epididymis protein 4 expression positively correlated with miR-21 and served as a prognostic indicator in ovarian cancerTumour Biol3783598365201610.1007/s13277-015-4672-826733162 LiLHuangKYouYFuXHuLSongLMengYHypoxia-induced miR-210 in epithelial ovarian cancer enhances cancer cell viability via promoting proliferation and inhibiting apoptosisInt J Oncol4421112120201410.3892/ijo.2014.236824715221 ZhuXShenHYinXLongLChenXFengFLiuYZhaoPXuYLiMIL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cellsOncotarget83915439166201710.18632/oncotarget.1661028388577 FanYFanJHuangLYeMHuangZWangYLiQHuangJIncreased expression of microRNA-196a predicts poor prognosis in human ovarian carcinomaInt J Clin Exp Pathol841324137201526097603 KoukourakisMIKontomanolisESotiropoulouMMitrakasADafaEPouliliouSSivridisEGiatromanolakiAIncreased soluble PD-L1 levels in the plasma of patients with epithelial ovarian cancer correlate with plasma levels of miR34a and miR200Anticancer Res3857395745201810.21873/anticanres.1291230275195 LiuJDouYShengMInhibition of microRNA-383 has tumor suppressive effect in human epithelial ovarian cancer through the action on caspase-2 geneBiomed Pharmacother8312861294201610.1016/j.biopha.2016.07.03827567588 DaiFZhangYChenYInvolvement of miR-29b signaling in the sensitivity to chemotherapy in patients with ovarian carcinomaHum Pathol4512851293201410.1016/j.humpath.2014.02.00824767251 XiaoMCaiJCaiLJiaJXieLZhuYHuangBJinDWangZLet-7e sensitizes epithelial ovarian cancer to cisplatin through repressing DNA double strand break repairJ Ovarian Res1024201710.1186/s13048-017-0321-828376831 LiXPanQWanXMaoYLuWXieXChengXMethylation-associated Has-miR-9 deregulation in paclitaxel-resistant epithelial ovarian carcinomaBMC Cancer15509201510.1186/s12885-015-1509-126152689 PaudelDZhouWOuyangYDongSHuangQGiriRWangJTongXMicroRNA-130b functions as a tumor suppressor by regulating RUNX3 in epithelial ovarian cancerGene5864855201610.1016/j.gene.2016.04.00127048832 DuanSDongXHaiJJiangJWangWYangJZhangWChenCMicroRNA-135a-3p is downregulated and serves as a tumour suppressor in ovarian cancer by targeting CCR2Biomed Pharmacother107712720201810.1016/j.biopha.2018.08.04430138893 ChenXDongCLawPTChanMTSuZWangSWuWKXuHMicroRNA-145 targets TRIM2 and exerts tumor-suppressing functions in epithelial ovarian cancerGynecol Oncol139513519201510.1016/j.ygyno.2015.10.00826472353 QinCZLouXYLvQLChengLWuNYHuLZhouHHMicroRNA-184 acts as a potential diagnostic and prognostic marker in epithelial ovarian cancer and regualtes cell proliferation, apoptosis and inflammationPharmazie70668673201526601424 LiangTLiLChengYRenCZhangGMicroRNA-194 promotes the growth, migration, and invasion of ovarian carcinoma cells by targeting protein tyrosine phosphatase nonreceptor type 12Onco Targets Ther943074315201610.2147/OTT.S9097627486333 WeiCZhangXHeSLiuBHanHSunXMicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathwayGene6372532201710.1016/j.gene.2017.09.01228890378 FuXLiYAlveroALiJWuQXiaoQPengYHuYLiXYanWMicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survivalOncotarget78063380654201610.18632/oncotarget.1301727811362 WuXRuanYJiangHXuCMicroRNA-424 inhibits cell migration, invasion, and epithelial mesenchymal transition by downregulating doublecortin-like kinase 1 in ovarian clear cell carcinomaInt J Biochem Cell Biol856674201710.1016/j.biocel.2017.01.02028161486 ZhangJLiuLSunYXiangJZhouDWangLXuHYangXDuNZhangMMicroRNA-520g promotes epithelial ovarian cancer progression and chemoresistance via DAPK2 repressionOncotarget72651626534201610.18632/oncotarget.853027049921 ZhangLLiZGaiFWangYMicroRNA-137 suppresses tumor growth in epithelial ovarian cancer in vitro and in vivoMol Med Rep1231073114201510.3892/mmr.2015.375625955305 LiuJJinSWangRMicroRNA-139 suppressed tumor cell proliferation, migration and invasion by directly targeting HDGF in epithelial ovarian cancerMol Med Rep1633793386201710.3892/mmr.2017.695628713954 XuLLiHSuLLuQLiuZMicroRNA-455 inhibits cell proliferation and invasion of epithelial ovarian cancer by directly targeting Notch1Mol Med Rep1697779785201710.3892/mmr.2017.766429039517 YanJJiangJMengXNXiuYLZongZHMiR-23b targets cyclin G1 and suppresses ovarian cancer tumorigenesis and progressionJ Exp Clin Cancer Res3531201610.1186/s13046-016-0307-126872615 LinJZhangLHuangHHuangYHuangLWangJHuangSHeLZhouYJiaWMiR-26b/KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and metastasis through downregulating OCT4Oncotarget62379323806201510.18632/oncotarget.436326204489 XuJJiangNShiHZhaoSYaoSShenHmiR-28-5p promotes the development and progression of ovarian cancer through inhibition of N4BP1Int J Oncol5013831391201710.3892/ijo.2017.397728350078 WangYZhangXTangWLinZXuLDongRLiYLiJZhangZLiXmiR-130a upregulates mTOR pathway by targeting TSC1 and is transactivated by NF-κB in high-grade serous ovarian carcinomaCell Death Differ2420892100201710.1038/cdd.2017.12928800130 WangLHeJXuHXuLLiNMiR-143 targets CTGF and exerts tumor-suppressing functions in epithelial ovarian cancerAm J Transl Res827162726201627398154 DongMYangPHuaFmiR-191 modulates malignant transformation of endometriosis through regulating TIMP3Med Sci Monit21915920201510.12659/MSM.89387225819812 NiuKShenWZhangYZhaoYLuYMiR-205 promotes motility of ovarian cancer cells via targeting ZEB1Gene574330336201510.1016/j.gene.2015.08.01726275944 DaiCXieYZhuangXYuanZMiR-206 inhibits epithelial ovarian cancer cells growth and invasion via blocking c-Met/AKT/mTOR signaling pathwayBiomed Pharmacother104763770201810.1016/j.biopha.2018.05.07729807226 XiaBYangSLiuTLouGmiR-211 suppresses epithelial ovarian cancer proliferation and cell-cycle progression by targeting Cyclin D1 and CDK6Mol Cancer1457201510.1186/s12943-015-0322-425889927 WuQRenXZhangYFuXLiYPengYXiaoQLiTOuyangCHuYMiR-221-3p targets ARF4 and inhibits the proliferation and migration of epithelial ovarian cancer cellsBiochem Biophys Res Commun49711621170201810.1016/j.bbrc.2017.01.00228057486 CaoLWanQLiFTangCMiR-363 inhibits cisplatin chemoresistance of epithelial ovarian cancer by regulating snail-induced epithelial-mesenchymal transitionBMB Rep51456461201810.5483/BMBRep.2018.51.9.10430037365 XiaBLiHYangSLiuTLouGMiR-381 inhibits epithelial ovarian cancer malignancy via YY1 suppressionTumour Biol3791579167201610.1007/s13277-016-4805-826768613 YuanJWangKXiMMiR-494 inhibits epithelial ovarian cancer growth by targeting c-MycMed Sci Monit22617624201610.12659/MSM.89728826908019 LiNZhaoXWangLZhangSCuiMHeJmiR-494 suppresses tumor growth of epithelial ovarian carcinoma by targeting IGF1RTumour Biol3777677776201610.1007/s13277-015-4603-826695144 ZhouQHZhaoYMJIALLZhangYMir-595 is a significant indicator of poor patient prognosis in epithelial ovarian cancerEur Rev Med Pharmacol Sci2142784282201729077170 ZhangSZhangJYLuLJWangCHWangLHMiR-630 promotes epithelial ovarian cancer proliferation and invasion via targeting KLF6Eur Rev Med Pharmacol Sci214542454721729131262 ShiCZhangZmiR-761 inhibits tumor progression by targeting MSI1 in ovarian carcinomaTumour Biol3754375443201610.1007/s13277-015-4377-z26563371 XieXHuangYChenLWangJmiR-221 regulates proliferation and apoptosis of ovarian cancer cells by targeting BMFOncol Lett1666976704201830405811 WenCLiuXMaHZhangWLiHmiR-338-3p suppresses tumor growth of ovarian epithelial carcinoma by targeting Runx2Int J Oncol4622772285201510.3892/ijo.2015.292925776272 SalemMO'BrienJABernaudoSShawerHYeGBrkićJAmlehAVanderhydenBCRefkyBYangBBmiR-590-3p promotes ovarian cancer growth and metastasis via a Novel FOXA2-versican pathwayCancer Res7841754190201810.1158/0008-5472.CAN-17-301429748371 LinZZhaoJWangXZhuXGongLOverexpression of microRNA-497 suppresses cell proliferation and induces apoptosis through targeting paired box 2 in human ovarian cancerOncol Rep3621012107201610.3892/or.2016.501227513319 LinMXiaBQinLChenHLouGS100A7 regulates ovarian cancer cell metastasis and chemoresistance through MAPK signaling and is targeted by miR-330-5pDNA Cell Biol37491500201810.1089/dna.2017.395329485916 ChenJLChenFZhangTTLiuNFSuppression of SIK1 by miR-141 in human ovarian cancer cell lines and tissuesInt J Mol Med3716011610201610.3892/ijmm.2016.255327081781 ZuberiMKhanIGandhiGRayPCSaxenaAThe conglomeration of diagnostic, prognostic and therapeutic potential of serum miR-199a and its association with clinicopathological features in epithelial ovarian cancerTumour Biol371125911266201610.1007/s13277-016-4993-226951510 GuanXZongZHChenSSangXBWuDDWangLLLiuYZhaoYThe role of miR-372 in ovarian carcinoma cell proliferationGene6241420201710.1016/j.gene.2017.04.04328456593 LiJLiDZhangWTumor suppressor role of miR-217 in human epithelial ovarian cancer by targeting IGF1ROncol Rep3516711679201610.3892/or.2015.449826708715 ZhangXLiuJZangDWuSLiuAZhuJWuGLiJJiangLUpregulation of miR-572 transcriptionally suppresses SOCS1 and p21 and contributes to human ovarian cancer progressionOncotarget61518015193201510.18632/oncotarget.373725893382 ZhouJGongGTanHDaiFZhuXChenYWangJLiuYChenPWuXWenJUrinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinomaOncol Rep3329152923201510.3892/or.2015.393725962395 ZhangXLiSDongCXieXZhangYKnockdown of long noncoding RNA NR_026689 inhibits proliferation and invasion and increases apoptosis in ovarian carcinoma HO-8910PM cellsOncol Res25259265201710.3727/096504016X1468503410391427624216 ZhuLGuoQLuXZhaoJShiJWangZZhouXCTD-2020K17.1, a novel long non-coding RNA, promotes migration, invasion, and proliferation of serous ovarian cancer cells in vitroMed Sci Monit2413291339201810.12659/MSM.90845629504606 QiuJJZhangXDTangXYZhengTTZhangYHuaKQElncRNA1, a long non-coding RNA that is transcriptionally induced by oestrogen, promotes epithelial ovarian cancer cell proliferationInt J Oncol51507514201710.3892/ijo.2017.403028714515 GaoYMengHLiuSHuJZhangYJiaoTLiuYOuJWangDYaoLLncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7bHum Mol Genet24841852201510.1093/hmg/ddu50225292198 WangYWangHSongTZouYJiangJFangLLiPHOTAIR is a potential target for the treatment of cisplatin-resistant ovarian cancerMol Med Rep1222112216201510.3892/mmr.2015.356225824616 LuCWZhouDDXieTHaoJLPantOPLuCBLiuXFHOXA11 antisense long noncoding RNA (HOXA11-AS): A promising lncRNA in human cancersCancer Med737923799201810.1002/cam4.157129992790 DuWFengZSunQLncRNA LINC00319 accelerates ovarian cancer progression through miR-423-5p/NACC1 pathwayBiochem Biophys Res Commun507198202201810.1016/j.bbrc.2018.11.00630442370 ShuCYanDMoYGuJShahNHeJLong noncoding RNA lncARSR promotes epithelial ovarian cancer cell proliferation and invasion by association with HuR and miR-200 familyAm J Cancer Res8981992201830034936 ChenSWuDDSangXBWangLLZongZHSunKXLiuBLZhaoYThe lncRNA HULC functions as an oncogene by targeting ATG7 and ITGB1 in epithelial ovarian carcinomaCell Death Dis8e3118201710.1038/cddis.2017.48629022892 QnboLGuanWRenWZhangLZhangJXuGMALAT1 affects ovarian cancer cell behavior and patient survivalOncol Rep3926442652201829693187 LinQGuanWRenWZhangLZhangJXuGMALAT1 affects ovarian cancer cell behavior and patient survivalOncol Rep3926442652201829693187 YanCJiangYWanYZhangLLiuJZhouSChengWLong noncoding RNA NBAT-1 suppresses tumorigenesis and predicts favorable prognosis in ovarian cancerOnco Targets Ther1019932002201710.2147/OTT.S12464528435289 LiuYWangYFuXLuZLong non-coding RNA NEAT1 promoted ovarian cancer cells' metastasis through regulation of miR-382-3p/ROCK1 axialCancer Sci10921882198201810.1111/cas.1364729790629 ChenSWangLLSunKXLiuYGuanXZongZHZhaoYLncRNA PCGEM1 induces ovarian carcinoma tumorigenesis and progression through RhoA pathwayCell Physiol Biochem4715781588201810.1159/00049093129949791 HuangKGengJWangJLong non-coding RNA RP11-552M11.4 promotes cells proliferation, migration and invasion by targeting BRCA2 in ovarian cancerCancer Sci10914281446201810.1111/cas.1355229478268 LiHLiuCLuZChenLWangJLiYMaHUpregulation of the long non-coding RNA SPRY4-IT1 indicates a poor prognosis and promotes tumorigenesis in ovarian cancerBiomed Pharmacother88529534201710.1016/j.biopha.2017.01.03728129625 LiTHZhangJJLiuSXChenYLong non-coding RNA taurine-upregulated gene 1 predicts unfavorable prognosis, promotes cells proliferation, and inhibits cells apoptosis in epithelial ovarian cancerMedicine (Baltimore)97e0575201810.1097/MD.000000000001057529742691 HongHHHouLKPanXWuCYHuangHLiBNieWLong non-coding RNA UCA1 is a predictive biomarker of cancerOncotarget74444244447201610.18632/oncotarget.1014227329842 ZhangLCaoXZhangLZhangXShengHTaoKUCA1 overexpression predicts clinical outcome of patients with ovarian cancer receiving adjuvant chemotherapyCancer Chemother Pharmacol77629634201610.1007/s00280-016-2963-426851957 QiuJJWangYLiuYLZhangYDingJXHuaKQThe long non-coding RNA ANRIL promotes proliferation and cell cycle progression and inhibits apoptosis and senescence in epithelial ovarian cancerOncotarget73247832492201610.18632/oncotarget.874427095571 CaoYShiHRenFJiaYZhangRLong non-coding RNA CCAT1 promotes metastasis and poor prognosis in epithelial ovarian cancerExp Cell Res359185194201710.1016/j.yexcr.2017.07.03028754469 HuaFLiCHChenXGLiuXPLong Noncoding RNA CCAT2 knockdown suppresses tumorous progression by sponging miR-424 in epithelial ovarian cancerOncol Res26241247201810.3727/096504017X1495394867541228550684 YimGWKimHJKimLKKimSWKimSNamEJKimYTLong Non-coding RNA HOXA11 antisense promotes cell proliferation and invasion and predicts patient prognosis in serous ovarian cancerCancer Res Treat49656668201710.4143/crt.2016.26327737536 KoutsakiMSpandidosDAZaravinosAEpithelial-mesenchymal transition-associated miRNAs in ovarian carcinoma, with highlight on the miR-200 family: Prognostic value and prospective role in ovarian cancer therapeuticsCancer Lett351173181201410.1016/j.canlet.2014.05.02224952258 SulaimanSAAb MutalibNSJamalRmiR-200c regulation of metastases in ovarian cancer: Potential role in epithelial and mesenchymal transitionFront Pharmacol7271201610.3389/fphar.2016.0027127601996 TengYSuXZhangXZhangYLiCNiuWLiuCQuKmiRNA-200a/c as potential biomarker in epithelial ovarian cancer (EOC): Evidence based on miRNA meta-signature and clinical investigationsOncotarget78162181633201610.18632/oncotarget.1315427835595 MuralidharGBarbolinaMThe miR-200 Family: Versatile players in epithelial ovarian cancerInt J Mol Sci161683316847201510.3390/ijms16081683326213923 ZuberiMKhanIMirRGandhiGRayPCSaxenaAUtility of serum miR-125b as a diagnostic and prognostic indicator and its alliance with a panel of tumor suppressor genes in epithelial ovarian cancerPLoS One11e0153902201610.1371/journal.pone.015390227092777 FaulCGersztenKEdwardsRLandSD'AngeloGKelleyJIIIPriceFA phase I/II study of hypofractionated whole abdominal radiation therapy in patients with chemoresistant ovarian carcinoma: Karnofsky score determines treatment outcomeInt J Radiat Oncol Biol Phys47749754200010.1016/S0360-3016(00)00446-610837960 IorioGCMartiniSArcadipaneFRicardiUFrancoPThe role of radiotherapy in epithelial ovarian cancer: A literature overviewMed Oncol3664201910.1007/s12032-019-1287-831165334 SorbeBConsolidation treatment of advanced ovarian carcinoma with radiotherapy after induction chemotherapyInt J Gynecol Cancer13(Suppl 2)S192S195200310.1111/j.1525-1438.2003.13359.x PangLGuoZDifferences in characteristics and outcomes between large-cell neuroendocrine carcinoma of the ovary and high-grade serous ovarian cancer: A retrospective observational cohort studyFront Oncol12891699202210.3389/fonc.2022.89169935600342 PatelSCFrandsenJBhatiaSGaffneyDImpact on survival with adjuvant radiotherapy for clear cell, mucinous, and endometriod ovarian cancer: The SEER experience from 2004 to 2011J Gynecol Oncol27e45201610.3802/jgo.2016.27.e4527329193 PestellKEMedlowCJTitleyJCKellandLRWaltonMICharacterisation Of The P53 Status, Bcl-2 expression and radiation and platinum drug sensitivity of a panel of human ovarian cancer cell linesInt J Cancer77913918199810.1002/(SICI)1097-0215(19980911)77:6<913::AID-IJC19>3.0.CO;2-19714063 ZielskeSPEpigenetic DNA methylation in radiation biology: On the field or on the sidelines?J Cell Biochem116212217201510.1002/jcb.2495925186310 KurreyNKJalgaonkarSPJoglekarAVGhanateADChaskarPDDoiphodeRYBapatSASnail and slug mediate radioresistance and chemoresistance by antagonizing p53-Mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cellsStem Cells2720592068200910.1002/stem.15419544473 LiuWJHuangYXWangWZhangYLiuBJQiuJGJiangBHLiuLZNOX4 signaling mediates cancer development and therapeutic resistance through HER3 in ovarian cancer cellsCells101647202110.3390/cells1007164734209278 ChenJJiaYJiaZHZhuYJinYMSilencing the expression of MTDH increases the radiation sensitivity of SKOV3 ovarian cancer cells and reduces their proliferation and metastasisInt J Oncol5321802190201830226587 ZhaoYLiuSWenYZhongLEffect of MicroRNA-210 on the growth of ovarian cancer cells and the efficacy of radiotherapyGynecol Obstet Invest867180202110.1159/00051177133260174 XingYCuiDWangSWangPXingXLiHOleuropein represses the radiation resistance of ovarian cancer by inhibiting hypoxia and microRNA-299-targetted heparanase expressionFood Funct828572864201710.1039/C7FO00552K28726915 MarquesCFerreira da SilvaFSousaINaveMChemotherapy-free treatment of recurrent advanced ovarian cancer: Myth or reality?Int J Gynecol Cancer33607618202310.1136/ijgc-2022-00371936446409 MarchettiCDe FeliceFRomitoAIacobelliVSassuCMCorradoGRicciCScambiaGFagottiAChemotherapy resistance in epithelial ovarian cancer: Mechanisms and emerging treatmentsSemin Cancer Biol77144166202110.1016/j.semcancer.2021.08.01134464704 FalzoneLBordonaroRLibraMSnapShot: Cancer chemotherapyCell18618161816.e1202310.1016/j.cell.2023.02.038 RaabMSanhajiMZhouSRödelFEl-BalatABeckerSStrebhardtKBlocking mitotic exit of ovarian cancer cells by pharmaceutical inhibition of the anaphase-promoting complex reduces chromosomal instabilityNeoplasia21363375201910.1016/j.neo.2019.01.00730851646 SwantonCNickeBSchuettMEklundACNgCLiQHardcastleTLeeARoyREastPKschischoMChromosomal instability determines taxane responseProc Natl Acad Sci USA10686718676200910.1073/pnas.081183510619458043 PradhanMRisbergBÅTropéCGvan de RijnMGilksCBLeeCHGross genomic alterations and gene expression profiles of high-grade serous carcinoma of the ovary with and without BRCA1 inactivationBMC Cancer10493201010.1186/1471-2407-10-49320843305 TangZYangJWangXZengMWangJWangAZhaoMGuoLLiuCLiDChenJActive DNA end processing in micronuclei of ovarian cancer cellsBMC Cancer18426201810.1186/s12885-018-4347-029661159 MordenCRFarrellACSliwowskiMLichtensztejnZAltmanADNachtigalMWMcManusKJChromosome instability is prevalent and dynamic in high-grade serous ovarian cancer patient samplesGynecol Oncol161769778202110.1016/j.ygyno.2021.02.03833714608 GorringeKLChinSFPharoahPStainesJMOliveiraCEdwardsPACaldasCEvidence that both genetic instability and selection contribute to the accumulation of chromosome alterations in cancerCarcinogenesis26923930200510.1093/carcin/bgi03215677628 BayaniJPaderovaJMurphyJRosenBZielenskaMSquireJADistinct patterns of structural and numerical chromosomal instability characterize sporadic ovarian cancerNeoplasia1010571065200810.1593/neo.0858418813350 BirkbakNJEklundACLiQMcClellandSEEndesfelderDTanPTanIBRichardsonALSzallasiZSwantonCParadoxical relationship between chromosomal instability and survival outcome in cancerCancer Res7134473452201110.1158/0008-5472.CAN-10-366721270108 HilleSReinDTRiffelmannMNeumannRSartoriusJPfütznerAKurbacherCMSchöndorfTBreidenbachMAnticancer drugs induce mdr1 gene expression in recurrent ovarian cancerAnticancer Drugs1710411044200610.1097/01.cad.0000231480.07654.b517001177 ZhangCWangMShiCShiFPeiCLong non-coding RNA Linc00312 modulates the sensitivity of ovarian cancer to cisplatin via the Bcl-2/Caspase-3 signaling pathwayBiosci Trends12309316201810.5582/bst.2018.0105229952351 CuiYQinLTianDWangTFanLZhangPWangZZEB1 Promotes chemoresistance to cisplatin in ovarian cancer cells by suppressing SLC3A2Chemotherapy63262271201810.1159/00049386430481785 SenTSenNBraitMBegumSChatterjeeAHoqueMORatovitskiESidranskyDNp63 confers tumor cell resistance to cisplatin through the AKT1 transcriptional regulationCancer Res7111671176201110.1158/0008-5472.CAN-10-148121266360 KumarSKumarAShahPPRaiSNPanguluriSKKakarSSMicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell linesJ Ovarian Res417201110.1186/1757-2215-4-1721939554 LeungAWYVeinotteCJMelongNMelongNOhMHChenKEnfieldKSSBackstromIWarburtonCYappDIn vivo validation of PAPSS1 (3′-phosphoadenosine 5′-phosphosulfate synthase 1) as a cisplatin-sensitizing therapeutic targetClin Cancer Res2365556566201710.1158/1078-0432.CCR-17-070028790117 KritschDHoffmannFSteinbachDJansenLMary PhotiniSGajdaMMosigASSonnemannJPetersSMelnikovaMTribbles 2 mediates cisplatin sensitivity and DNA damage response in epithelial ovarian cancerInt J Cancer14116001614201710.1002/ijc.3086028670762 NamEJKimSLeeTSKimHJLeeJYKimSWKimJHKimYTPrimary and recurrent ovarian high-grade serous carcinomas display similar microRNA expression patterns relative to those of normal ovarian tissueOncotarget77052470534201610.18632/oncotarget.1204527655640 ChongGOJeonHSHanHSSonJWLeeYHHongDGLeeYSChoYDifferential MicroRNA expression profiles in primary and recurrent epithelial ovarian cancerAnticancer Res7261126172015 ChongGOJeonHSHanHSSonJWLeeYHHongDGParkHJLeeYSChoYLOverexpression of microRNA-196b accelerates invasiveness of cancer cells in recurrent epithelial ovarian cancer through regulation of homeobox A9Cancer Genomics Proteomics14137142201710.21873/cgp.2002628387653 ZhouYWangMWuJJieZChangSShuangTThe clinicopathological significance of miR-1307 in chemotherapy resistant epithelial ovarian cancerJ Ovarian Res823201510.1186/s13048-015-0143-525887170 ChenCHuYLiLNRP1 is targeted by miR-130a and miR-130b, and is associated with multidrug resistance in epithelial ovarian cancer based on integrated gene network analysisMol Med Rep13188196201610.3892/mmr.2015.455626573160

Natural history of ovarian carcinoma. Ovarian carcinoma is a heterogeneous type of cancer. Five subtypes of ovarian carcinomas originate in different forms. Origin tissues are enlisted in the periphery of the image and ovarian carcinomas are enlisted near the image core, similar to the nuclear ovarian carcinoma archetype. The transformation of the cells of the ovarian carcinoma origin can be described as follows: Fallopian tube cells originate HGSOC. Superficial cells of the ovary originate CCC. The origin of colorectal or stomach cells that develop in MC remains to be determined due to their tissue similitudes Endometrial cells originate EC. Fallopian tube cells or ovary cells originate LGSOC. Created by BioRender.com. Accessed on 09/2024. HGSOC, high-grade serous ovarian carcinoma; CCC, clear cell carcinoma; LGSOC, low-grade serous ovarian carcinoma; EC, endometrioid carcinoma; MC, mucinous carcinoma.

DNA methylation and RNA transcripts in the diagnosis and prognosis of ovarian carcinomas. Heterogeneous DNA methylation corresponds to heterogeneous ovarian carcinomas. RNA expression of the transcripts is associated with DNA methylation. Certain studies have characterized DNA methylation and RNA transcription of specific genes in ovarian carcinoma subtypes. Generally, with a few exceptions, different RNAs are affected by the methylation status of the DNA. For example, molecular diagnosis of HGSOC is performed by chromosome 9 locus Chr9q21.31 that contains unmethylated DNA; an overexpression of the large non-coding RNA ARSR is noted. By contrast, in the locus Chr9q34.11, which contains a methylated DNA, downregulation of miR199b-59p expression is noted. Created by BioRender.com. Accessed on 09/2024. HGSOC, high-grade serous ovarian carcinoma subtype; miR, microRNA.

The variability of ncRNAs is related to clinical pathogenesis and resistance in ovarian carcinoma. The differential expression status between ovarian cancer and normal tissue has been associated with clinical outcomes such as ovarian carcinoma subtype, progression, metastases, radioresistance and chemoresistance, and more importantly, in the disease prognosis of the patients. For example, the ncRNA expression levels of the ovarian carcinoma type indicated that the aforementioned genes were located in a specific locus from a unit of chromosome 19. Overexpression of UCA1, a large non-coding RNA located in locus 19p13.12 and downregulation of the Let7E miR levels located in 19q13.41 were associated with poor prognosis. Similarly, overexpression of miR330-5p in 19q13.32 was associated with lymph node invasion and downregulation of miR520g levels was associated with resistance to chemotherapy. ncRNAs overexpressed are shown in red and the downregulated RNA transcript are shown in green. ncRNA, non-coding RNA; miR, microRNA.

Characterization of DNA methylation loci in ovarian carcinomas.

First author/s, year Ovarian carcinoma subtype Locus chromosome Gene on the locus Methods Status in ovarian carcinoma (Refs.)
Feng et al, 2008 EOC 3q13.33 and 19q13.43 ARH1 and PEG3 Sodium bisulfite and pyrosequencing Hypermethylated (29)
Link et al, 2013 EOC 20q13.31 BORIS/CTCFL Sodium bisulfite and pyrosequencing Unmethylated (30)
Wang et al, 2013 EOC 17q21.31 BRCA1 Sodium bisulfite and RT-qPCR Hypermethylated (31)
Abou-Zeid et al, 2011; Bhagat et al, 2014 EOC 9p21.3 CDKN2A Sodium bisulfite and RT-qPCR Hypermethylated (32,33)
Yang et al, 2013 EOC 8p21.1 Clusterin Sodium bisulfite and RT-qPCR Unmethylated (34)
Zhang et al, 2015 EOC Xq26.3 CT45 Sodium bisulfite and pyrosequencing Unmethylated (35)
Wang et al, 2017 EOC 11q25 OPCML Sodium bisulfite and RT-qPCR Hypermethylated (36)
Kaur et al, 2016 EOC 9q21.33 and 13q34 DAPK1 and SOX1 Sodium bisulfite and RT-qPCR Hypermethylated (37)
Rattanapan et al, 2018 HGSOC 9q34.3 EGFL7 Sodium bisulfite and pyrosequencing Hypermethylated (38)
da Conceição Braga et al, 2014 EOC 18q21.33 and 8p21.3 BCL2 and TRAIL2-R2 Sodium bisulfite and RT-qPCR Hypermethylated (39)
Bonito et al, 2016 EOC 4p16.2 MSX1 Sodium bisulfite and RT-qPCR Hypermethylated (40)
Kardum et al, 2017; Suzuki et al, 2008 EOC 14q23.2 ER-β Sodium bisulfite and RT-qPCR. Hypermethylated (41,42)
Sodium bisulfite and pyrosequencing
Baranova et al, 2018 HGSOC 13q21.1 PCDH17 Sodium bisulfite and RT-qPCR. Hypermethylated (43)
Sodium bisulfite and pyrosequencing
Ding et al, 2016 EOC 11p14.3 FANCF Sodium bisulfite and pyrosequencing Hypermethylated (44)
Gozzi et al, 2016 EOC 1p12 TBX15 Sodium bisulfite and pyrosequencing Hypermethylated (45)
Choi et al, 2006 EOC 3p21.31 RASSF1A Sodium bisulfite and RT-RT-qPCR Hypermethylated (46)
Häfner et al, 2016 EOC 1p36.11 and 1p36.12 RUNX3 and CAMK2N1 Sodium bisulfite and RT-qPCR Hypermethylated (47)
Jin et al, 2018 EOC 3p14.3 Wnt5a Sodium bisulfite and RT-qPCR Hypermethylated (48)

EOC, epithelial ovarian cancer; HGSOC, high-grade serous ovarian carcinoma; RT-qPCR, reverse transcription-quantitative PCR.

Hyper-methylated miRNAs locus in ovarian carcinoma.

Locus chromosome Non-coding RNA expressed in locus DNA status methylation in locus RNA expression of locus
11q24.1 miR-125-1 Hypermethylated Downregulated
14q32.2 miR-127 Hypermethylated Downregulated
11p11.2 miR-129-2 Hypermethylated Downregulated
1p21.3 miR-137 Hypermethylated Downregulated
17q11.2 miR-193a Hypermethylated Downregulated
14q32.2 MEG3 Hypermethylated Downregulated

miR, microRNA. All dates referenced in this table from (53).

microRNAs expression associated with cancer functions derived from locus and target locus RNAs probed in specific ovarian carcinoma subtypes.

First author/s, year Ovarian carcinoma subtype Associated with Locus of the miRNA microRNA RNA regulation Locus of the target RNA from the locus target (Refs.)
Nymoen et al, 2016 EOC Poor prognosis 7q32.3 29a Down 2p23.3 DNMT3A (66)
Arts et al, 2017 HGSOC HGSOC Xq12 223 Up 12q13.12 SMARCD1 (67)
Ying et al, 2016 EOC Poor prognosis, clinical stage III and IV clinical grade 11q24.1 125b Down 9q34.11 SET (99)
Zhu et al, 2017 EOC II and III lymph node metastasis distant metastasis 11q24.1 125b Up 9q34.11 SET (100)
Teng et al, 2015 EOC Poor prognosis 1p36.33 29b Down 1q21.2, 19q13.2 and 1q43 Mcl-1, AKT2 and AKT3 (101)
Cao et al, 2015; Katepanakis et al, 2015; Meng et al, 2016 EOC Poor prognosis stage grade 1p36.33 200a/200b/200c Up (102–104)
Du et al, 2017 EOC EOC 12p13.31 551a Down 22q11.22/14q32.33 MAPK/AKT (105)
Chaluvally-Raghavan et al, 2016 EOC Poor prognosis 1p36.32 551b-3p Up 17q21.2 STAT3 (68)
Chen et al, 2015 EOC Advanced stages High grade 3q26.2 490-3p Up 10q21.2 CDK1 (106)
Shuang et al, 2015 EOC Chemotherapy resistant 14q32.31 134 Down 3q29 Pak2 (107)
Zou et al, 2015 EOC Stage histology 15q24.1 630 Down 10q23.31 PTEN (108)
Zhang et al, 2016 EOC EOC 5q32 143-3p Down 18p11.22 RALBP1 (109)
Zhang et al, 2018 EOC Stage lymph node metastasis 21q21.1 Let-7c Down 3p21.31 CDC25a (110)
Liu et al, 2014 EOC Poor prognosis stage 9q34.11 199b-5p Down 20p12.2-9q34.3 JAG1-NOTCH1 (111)
Ma et al, 2016 EOC EOC 8p11.21 486-5p Down 13q14.3 OLFM4 (65)
Kobayashi et al, 2018 HGSOC Advanced stages 1p36.13 1290 Up - Serum (112)
Zhao, et al, 2015. EOC Complete response 14q32.2 136 Up - DNA repair and apoptosis (69)
Zhao et al, 2014 EOC Complete/poor response Xq25 224-5p Down 3p21.1 PRKCD (113)
Wang et al, 2018 HGSOC EOC 6q13 13p.33 30a-5p 200a-5p Up 6p21.2 P21 (64)
Chen et al, 2016 EOC Stage grade relapse 17q23.1 21 Up 20q13.2 HE4 (114)
Li et al, 2014 EOC Stage III and IV 11p15.5 210 Up 14q23.2 HIF (115)
Zhu et al, 2017 EOC Resistance 9p21.12 204 Up - - (116)
Fan et al, 2015 EOC Poor prognosis stage III and IV tumor size metastasis 17q21.32 196a Up 21q22.12 RUNX1 (117)
Koukorakis et al, 2018 HGSOC HGSOC 1p36.22 1p36.33 34a 200 Down Up 9p24.1 PD-L1 (118)
Liu et al, 2016 EOC EOC 8p22 383 Up 7q34 Caspase-2 (119)
Dai et al, 2014 EOC Stages III and IV relapse 7q32.3 29b Down 4q21.3 MAPK10 (120)
Xiao et al, 2017 EOC Therapy sensible poor prognosis 19q13.41 Let-7e Down 17q21.31 and 15q15.1 BRCA1 and RAD51 (121)
Li et al, 2015 EOC Therapy sensible poor prognosis metastasis 1q22 9 Down Up 5q34 and 16q22.1 CCNG1 and E-cadherin (122)
Paudel et al, 2016 EOC Stages III and IV 22q11.21 130b Down 1q36.11 RUNX3 (123)
Duan et al, 2018 EOC Poor prognosis 3p21.2 135a-3p Down 3p21.31 CCR2 (124)
Chen et al, 2015 EOC EOC 5q32 145 Down 4q31.3 TRIM2 (125)
Qin et al, 2015 EOC Poor prognosis stages III and IV 15q25.1 184 Down - - (126)
Liang et al, 2016 EOC EOC 1q41 194 Up 7q11.23 PTPN12 (127)
Wei et al, 2017 EOC EOC 6p21.32 219-5p Down 7p21.1 Twist (128)
Fu et al, 2016 EOC Grades II and III poor prognosis Xp11.3 222-3p Down 14q32.33 and 10q23.31 AKT and PTEN (129)
Wu et al, 2017 CCC CCC 424 Down 13q13.3 DCLK1 (130)
Chen et al, 2015 EOC Advanced stages Grades II and III Xq26.3 490-3p Down 10q21.2 CDK1 (106)
Zhang et al, 2016 EOC Poor prognosis stage III and IV ascites lymph node metastasis grade III tumor size chemoresistance 19q13.42 520g - 15q22.31 DAPK2 (131)
Zhang et al, 2016 EOC Stage III and IV lymph node metastasis 1p21.3 137 Down - - (132)
Liu et al, 2017 EOC EOC 11q13.4 139 Down 1q23.1 HDGF (133)
Xu et al, 2017 EOC Stage III and IV tumor size lymph node metastasis 9q32 455 Down 9q34.3 NOTCH1 (134)
Yan et al, 2016 EOC Age 9q22.32 23b Down 5q34 CCNG1 (135)
Lin et al, 2015 EOC Poor prognosis stages III and IV distant metastasis recurrence 2q35 26b Down 17q24.2 KPNA2 (136)
Xu et al, 2017 EOC EOC 3q28 28-5p Up 16q12.1 N4BP1 (137)
Wang et al, 2017 HGSOC Advanced stages 11q21.1 130a Down 9q34 TSC1 (138)
Wang et al, 2016 EOC Stages III and IV Grades II and III lymph node metastasis 5q32 143 Down 6q23.2 CTGF (139)
Dong et al, 2015 EC EC 3p21.31 191 Up 9q21.33 DAPK1 (140)
Niu et al, 2015 EOC Stages III and IV High grade 1q32.2 205 Up 10p11.22 ZEB1 (141)
Dai et al, 2018 EOC EOC 6p12.2 206 Down 1p36.22 mTOR (142)
Xia et al, 2015 HGSOC, CCC Tumors 15q13.3 211 Down 11q13.3 and 7q21.2 Cyclin D1 and CDK6 (143)
Wu et al, 2018 EOC Poor prognosis death Xp11.3 221-3p Down 3p14.3 ARF4 (144)
Cao et al, 2018 EOC Resistant Xq26.2 363 Down 20q13.3 Snail (145)
Xia et al, 2016 EOC Stages III and IV 8p22 383 Down 14q32.2 YY1 (146)
Grades II and III
Yuan et al, 2016; Li et al 2016 EOC Stages III and IV Grades II and III lymph node metastasis 14q32.31 494 Down 8q24.21 and 15q26.3 c-Myc and IGF1R (147,148)
Zhou et al, 2017 EOC Stage III and IV Grade II and III distant metastasis 7q36.3 595 Down - - (149)
Zhang et al, 2017 EOC EOC 15q24.1 630 Up 10p15.2 KLF6 (150)
Shi et al, 2016 EOC EOC 1p32.3 761 Down 12q24.31 MSI1 (151)
Xie et al, 2018 EOC EOC Xp11.3 221 Up 15q15.1 BMF (152)
Wen et al, 2015 EOC Stage III and IV Grade II and III lymph node metastasis 17q25.3 338-3p Down 6p21.1 RUNX2 (153)
Salem et al, 2018 EOC Grades II and III 7q11.23 590-3p Up 20p11.21 FOXA2 (154)
Lin et al, 2016 EOC EOC 17p13.1 497 Down 10q24.31 PAX2 (155)
Lin et al, 2018 EOC Stage grade lymph node metastasis 19q13.32 330-5p Up 22q11.22 MAPK (156)
Chen et al, 2016 EOC EOC 12p13.31 141 Down 21q22.3 SIK1 (157)
Zuberi et al, 2016 EOC Stage lymph node metastasis 19p13.2 199a Down - - (158)
Agostini et al, 2018 MC MC 11q13.1 and 1q41 192 and 215 Down - - (78)
Guan et al, 2017 EOC EOC 19q13.42 372 Down 8q24.13, 13q12.11, 5q35.3, 10q21.1 and 13q13.3 ATAD2, LATS2, P62, DKK1 and cyclinA1 (159)
Li et al, 2016 EOC Advanced stages High grade lymph node metastasis 2p16.1 217 Down 15q26.3 IGF1R (160)
Zhang et al, 2015 EOC Poor prognosis 4p15.33 572 Up 16p13.13 and 6p21.2 SOCS1 and P21 (161)
Zhou et al, 2015 SOC Preoperative 6q13 30a-5p Up - - (162)

EOC, epithelial ovarian cancer; HGSOC, high grade serous ovarian carcinoma; CCC, clear cells carcinoma; MC, mucinous carcinoma; EC, endometrioid carcinoma. High grade, grades II and III. Advanced stages, III and IV.

Long non-coding RNAs expression associated to cancer functions derived from locus probed in specific ovarian carcinoma subtypes.

First author/s, year Ovarian cancer subtype Associated with Locus LncRNA Regulation (Refs.)
Xi et al, 2017 EOC Poor prognosis stage grade lymph node metastasis 5q11.2 lncBRM Up (92)
Zhang et al, 2017 EOC EOC 1p21.2 NR_026689 Up (163)
Wang et al, 2017 EOC Favorable prognosis stage Lymph node metastasis 2q34 CPS1-IT1 Down (97)
Zhu et al, 2018 EOC Metastasis CA-125 levels 2p25.1 CTD2020K17.1 Up (164)
Qiu et al, 2017 EOC EOC 1q32.1 ElncRNA1 Up (165)
Gao et al, 2015 EOC EOC 10q23.1 HOST2 Up (166)
Wang et al, 2015 EOC Poor prognosis Stage Histological grade Residual tumor Lymph node metastasis 12q13.13 HOTAIR Up (167)
Lu et al, 2018 HGSOC Poor prognosis 7p15.2 HOXA11-AS Up (168)
Zhang et al, 2017 EOC Poor prognostic stage lymph node metastasis 2q31.1 HOXD-AS1 Up (93)
Du et al, 2018 EOC Poor prognosis 21q22.3 LINC00319 Up (169)
Shu et al, 2018 EOC Poor prognosis stage grade lymph metastasis distant metastasis 9q21.31 ARSR Up (170)
Chen et al, 2017 EOC EOC 6p24.3 HULC Up (171)
Liu et al, 2018 EOC Stage tumor size distant metastasis 6p21 LncSox4 Up (94)
Qunbo et al, 2018; Lin et al, 2018 EOC Poor prognostic 11q13.1 MALAT1 Up (172,173)
Yan et al, 2018 EOC Poor prognostic stage depth of invasion lymph node metastasis distant metastasis 2q31.1 MLK7-AS1 Up (95)
Yan et al, 2017 EOC Favorable prognosis tumor size 6p22.3 NBAT-1 Down (174)
Liu et al, 2018 EOC Poor prognostic stage grade residual tumor metastasis 11q13.1 NEAT1 Up (175)
Chen et al, 2018 EOC Grade 2q32.3 PCGEM1 Up (176)
Huang et al, 2018 EOC Stage grade tumor size 1p13.2 RP11-552M11.4 Up (177)
Li et al, 2017 EOC Poor prognosis stage grade lymph node metastasis 5q31.3 SPRY4-IT1 Up (178)
Zhu et al, 2017 EOC Favorable prognosis stage grade lymph node metastasis CA-125 levels 2q35 lncRNA-TUBA4B Down (98)
Li et al, 2018 EOC EOC poor prognosis stage grade tumor size 22q12.2 lncRNA-TUG1 Up (179)
Hong et al, 2016 EOC Poor prognostic stage lymph node metastasis chemotherapy response 19p13.12 lncRNA-UCA1 Up (180,181)
Qiu et al, 2016 EOC Poor prognosis stage grade 9p21.3 ANRIL Up (182)
Zhang et al, 2018 EOC EOC 10q26.11 CASC2 Down (90)
Cao et al, 2017 EOC EOC 8q24.21 CCAT1 Up (183)
Hua et al, 2018 EOC EOC 8q24.21 CCAT2 Up (184)

EOC, epithelial ovarian cancer; HGSOC, high-grade serous ovarian carcinoma.