A gene interaction network‑based method to measure the common and heterogeneous mechanisms of gynecological cancer

Wang,Mingyuan; Li,Liping; Liu,Jinglan; Wang,Jinjin

doi:10.3892/mmr.2018.8961

A gene interaction network‑based method to measure the common and heterogeneous mechanisms of gynecological cancer

Authors:
- Mingyuan Wang
- Liping Li
- Jinglan Liu
- Jinjin Wang
View Affiliations

Affiliations: The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, Hunan 412000, P.R. China
Published online on: May 3, 2018 https://doi.org/10.3892/mmr.2018.8961
Pages: 230-242
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gynecological malignancies are a leading cause of mortality in the female population. The present study intended to identify the association between three severe types of gynecological cancer, specifically ovarian cancer, cervical cancer and endometrial cancer, and to identify the connective driver genes, microRNAs (miRNAs) and biological processes associated with these types of gynecological cancer. In the present study, individual driver genes for each type of cancer were identified using integrated analysis of multiple microarray data. Gene Ontology (GO) has been used widely in functional annotation and enrichment analysis. In the present study, GO enrichment analysis revealed a number of common biological processes involved in gynecological cancer, including ‘cell cycle’ and ‘regulation of macromolecule metabolism’. Kyoto Encyclopedia of Genes and Genomes pathway analysis is a resource for understanding the high‑level functions and utilities of a biological system from molecular‑level information. In the present study, the most common pathway was ‘cell cycle’. A protein‑protein interaction network was constructed to identify a hub of connective genes, including minichromosome maintenance complex component 2 (MCM2), matrix metalloproteinase 2 (MMP2), collagen type I α1 chain (COL1A1) and Jun proto‑oncogene AP‑1 transcription factor subunit (JUN). Survival analysis revealed that the expression of MCM2, MMP2, COL1A1 and JUN was associated with the prognosis of the aforementioned gynecological cancer types. By constructing an miRNA‑driver gene network, let‑7 targeted the majority of the driver genes. In conclusion, the present study demonstrated a connection model across three types of gynecological cancer, which was useful in identifying potential diagnostic markers and novel therapeutic targets, in addition to in aiding the prediction of the development of cancer as it progresses.

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1	Li XY and Wang X: The role of human cervical cancer oncogene in cancer progression. Int J Clin Exp Med. 8:8363–8368. 2015.PubMed/NCBI
2	Nisker JA: Screening for endometrial cancer. Can Fam Physician. 29:961–965. 1983.PubMed/NCBI
3	Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, Wolk A, Wentzensen N, Weiss NS, Webb PM, et al: Type I and II endometrial cancers: Have they different risk factors? J Clin Oncol. 31:2607–2618. 2013. View Article : Google Scholar : PubMed/NCBI
4	Wright JD: Take 'em or leave 'em: Management of the ovaries in young women with endometrial cancer. Gynecol Oncol. 131:287–288. 2013. View Article : Google Scholar : PubMed/NCBI
5	Lukk M, Kapushesky M, Nikkilä J, Parkinson H, Goncalves A, Hube W, Ukkonen E and Brazma A: A global map of human gene expression. Nat Biotechnol. 28:322–324. 2010. View Article : Google Scholar : PubMed/NCBI
6	Cancer Genome Atlas Research Network, . McLendon R, Friedman A, Bigner D, Van Meir EG, Brat DJ, Mastrogianakis GM, Olson JJ, Mikkelsen T, Lehman N, et al: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 455:1061–1068. 2008. View Article : Google Scholar : PubMed/NCBI
7	Cancer Genome Atlas Research Network: Integrated genomic analyses of ovarian carcinoma. Nature. 474:609–615. 2011. View Article : Google Scholar : PubMed/NCBI
8	Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, et al: Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 44:694–698. 2012. View Article : Google Scholar : PubMed/NCBI
9	Liu P, Morrison C, Wang L, Xiong D, Vedell P, Cui P, Hua X, Ding F, Lu Y, James M, et al: Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing. Carcinogenesis. 33:1270–1276. 2012. View Article : Google Scholar : PubMed/NCBI
10	Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD, Raine K, Jones D, Hinton J, Marshall J, Stebbings LA, et al: Mutational processes molding the genomes of 21 breast cancers. Cell. 149:979–993. 2012. View Article : Google Scholar : PubMed/NCBI
11	Baudot A, Real FX, Izarzugaza JM and Valencia A: From cancer genomes to cancer models: Bridging the gaps. EMBO Rep. 10:359–366. 2009. View Article : Google Scholar : PubMed/NCBI
12	Kreeger PK and Lauffenburger DA: Cancer systems biology: A network modeling perspective. Carcinogenesis. 31:2–8. 2010. View Article : Google Scholar : PubMed/NCBI
13	Lee S, Stewart S, Nagtegaal I, Luo J, Wu Y, Colditz G, Medina D and Allred DC: Differentially expressed genes regulating the progression of ductal carcinoma in situ to invasive breast cancer. Cancer Res. 72:4574–4586. 2012. View Article : Google Scholar : PubMed/NCBI
14	Wray CJ, Ko TC and Tan FK: Secondary use of existing public microarray data to predict outcome for hepatocellular carcinoma. J Surg Res. 188:137–142. 2014. View Article : Google Scholar : PubMed/NCBI
15	Barrett T, Troup DB, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, et al: NCBI GEO: Archive for functional genomics data sets-10 years on. Nucleic Acids Res. 39:(Database Issue). D1005–D1010. 2011. View Article : Google Scholar : PubMed/NCBI
16	Chung VY, Tan TZ, Tan M, Wong MK, Kuay KT, Yang Z, Ye J, Muller J, Koh CM, Guccione E, et al: GRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification. Sci Rep. 6:199432016. View Article : Google Scholar : PubMed/NCBI
17	Halabi NM, Martinez A, Al-Farsi H, Mery E, Puydenus L, Pujol P, Khalak HG, McLurcan C, Ferron G, Querleu D, et al: Preferential allele expression analysis identifies shared germline and somatic driver genes in advanced ovarian cancer. PLoS Genet. 12:e10058922016. View Article : Google Scholar : PubMed/NCBI
18	Espinosa AM, Alfaro A, Roman-Basaure E, Guardado-Estrada M, Palma Í, Serralde C, Medina I, Juárez E, Bermúdez M, Márquez E, et al: Mitosis is a source of potential markers for screening and survival and therapeutic targets in cervical cancer. PLoS One. 8:e559752013. View Article : Google Scholar : PubMed/NCBI
19	Shaul YD, Yuan B, Thiru P, Nutter-Upham A, McCallum S, Lanzkron C, Bell GW and Sabatini DM: MERAV: A tool for comparing gene expression across human tissues and cell types. Nucleic Acids Res. 44:D560–D566. 2016. View Article : Google Scholar : PubMed/NCBI
20	R Development Core Team, . R: A language and environment for statistical computingR Foundation for Statistical Computing. Vienna, Austria: 2017
21	Prasad Keshava TS, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, Telikicherla D, Raju R, Shafreen B, Venugopal A, et al: Human protein reference database-2009 update. Nucleic Acids Res. 37:(Database Issue). D767–D772. 2009. View Article : Google Scholar : PubMed/NCBI
22	Jiang Q, Wang Y, Hao Y, Juan L, Teng M, Zhang X, Li M, Wang G and Liu Y: miR2Disease: A manually curated database for microRNA deregulation in human disease. Nucleic Acids Res. 37:(Database Issue). D98–D104. 2009. View Article : Google Scholar : PubMed/NCBI
23	Vlachos IS, Paraskevopoulou MD, Karagkouni D, Georgakilas G, Vergoulis T, Kanellos I, Anastasopoulos IL, Maniou S, Karathanou K, Kalfakakou D, et al: DIANA-TarBase v7.0: Indexing more than half a million experimentally supported miRNA:mRNA interactions. Nucleic Acids Res. 43:(Database Issue). D153–D159. 2015. View Article : Google Scholar : PubMed/NCBI
24	Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC and Lempicki RA: DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol. 4:P32003. View Article : Google Scholar : PubMed/NCBI
25	Kaimal V, Bardes EE, Tabar SC, Jegga AG and Aronow BJ: ToppCluster: A multiple gene list feature analyzer for comparative enrichment clustering and network-based dissection of biological systems. Nucleic Acids Res. 38:W96–W102. 2010. View Article : Google Scholar : PubMed/NCBI
26	Altermann E and Klaenhammer TR: PathwayVoyager: Pathway mapping using the Kyoto encyclopedia of genes and genomes (KEGG) database. BMC Genomics. 6:602005. View Article : Google Scholar : PubMed/NCBI
27	Stamoulis C and Betensky RA: A novel signal processing approach for the detection of copy number variations in the human genome. Bioinformatics. 27:2338–2345. 2011. View Article : Google Scholar : PubMed/NCBI
28	Miller CA, Settle SH, Sulman EP, Aldape KD and Milosavljevic A: Discovering functional modules by identifying recurrent and mutually exclusive mutational patterns in tumors. BMC Med Genomics. 4:342011. View Article : Google Scholar : PubMed/NCBI
29	Ciriello G, Cerami E, Sander C and Schultz N: Mutual exclusivity analysis identifies oncogenic network modules. Genome Res. 22:398–406. 2012. View Article : Google Scholar : PubMed/NCBI
30	Vandin F, Upfal E and Raphael BJ: De novo discovery of mutated driver pathways in cancer. Genome Res. 22:375–385. 2012. View Article : Google Scholar : PubMed/NCBI
31	Tsaniras Champeris S, Kanellakis N, Symeonidou IE, Nikolopoulou P, Lygerou Z and Taraviras S: Licensing of DNA replication, cancer, pluripotency and differentiation: An interlinked world? Semin Cell Dev Biol. 30:174–180. 2014. View Article : Google Scholar : PubMed/NCBI
32	Pruitt SC, Bailey KJ and Freeland A: Reduced Mcm2 expression results in severe stem/progenitor cell deficiency and cancer. Stem Cells. 25:3121–3132. 2007. View Article : Google Scholar : PubMed/NCBI
33	Simon NE and Schwacha A: The Mcm2-7 replicative helicase: A promising chemotherapeutic target. Biomed Res Int. 2014:5497192014. View Article : Google Scholar : PubMed/NCBI
34	Pittayapruek P, Meephansan J, Prapapan O, Komine M and Ohtsuki M: Role of matrix metalloproteinases in photoaging and photocarcinogenesis. Int J Mol Sci. 17:pii: E8682016. View Article : Google Scholar
35	Chan TF, Poon A, Basu A, Addleman NR, Chen J, Phong A, Byers PH, Klein TE and Kwok PY: Natural variation in four human collagen genes across an ethnically diverse population. Genomics. 91:307–314. 2008. View Article : Google Scholar : PubMed/NCBI
36	Bosman FT and Stamenkovic I: Functional structure and composition of the extracellular matrix. J Pathol. 200:423–428. 2003. View Article : Google Scholar : PubMed/NCBI
37	Uitto VJ and Larjava H: Extracellular matrix molecules and their receptors: An overview with special emphasis on periodontal tissues. Crit Rev Oral Biol Med. 2:323–354. 1991. View Article : Google Scholar : PubMed/NCBI
38	Deyl Z, Miksik I and Eckhardt A: Preparative procedures and purity assessment of collagen proteins. J Chromatogr B Analyt Technol Biomed Life Sci. 790:245–275. 2003. View Article : Google Scholar : PubMed/NCBI
39	Dai J, Wang T, Wang W, Zhang S, Liao Y and Chen J: Role of MAPK7 in cell proliferation and metastasis in ovarian cancer. Int J Clin Exp Pathol. 8:10444–10451. 2015.PubMed/NCBI
40	Lee YS and Dutta A: The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 21:1025–1030. 2007. View Article : Google Scholar : PubMed/NCBI
41	Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, Wang Y, Qian Z, Jin J, Zhang Y, et al: MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA. 104:19971–19976. 2007. View Article : Google Scholar : PubMed/NCBI