Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
November-2018 Volume 40 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2018 Volume 40 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Profile and validation of dysregulated long non‑coding RNAs and mRNAs in ovarian cancer

  • Authors:
    • Yan‑Ming Lu
    • Yue Wang
    • Shi‑Qi Liu
    • Meng‑Ya Zhou
    • Ya‑Ru Guo
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology and Obstetrics, The Affiliated Shengjing Hospital, China Medical University, Shenyang, Liaoning 110003, P.R. China
  • Pages: 2964-2976
    |
    Published online on: August 17, 2018
       https://doi.org/10.3892/or.2018.6654
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The dysregulation of long non‑coding RNAs (lncRNAs) is associated with cancer development. The present study profiled differentially expressed lncRNAs in ovarian cancer (OC) versus normal ovarian tissues (NT) and investigated their potential functions in gene expression. OC tissues from 30 patients and NT specimens from 20 non‑tumor patients were collected, and 5 cases of tumor and NT were subjected to lncRNA and mRNA microarray analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to verify microarray data in all 30 cases. There were 2,870 differentially expressed lncRNAs (795 upregulated and 2,075 downregulated) and 2,658 differentially expressed mRNAs (1,014 upregulated and 1,644 downregulated) in OC. A total of 4 upregulated and 4 downregulated lncRNAs were validated using RT‑qPCR. The data demonstrated that, with the exception of ENST00000453838 and ENST00000505048, the lncRNAs were consistent with the microarray data. Another differentially expressed lncRNA (BC041954) was assessed using independent tissue samples, and results further supported the microarray data. Moreover, GO analysis showed that the upregulated genes were involved in the ‘development of the cell anatomical structure’ (GO: 0048856; P=5.46x10‑6), ‘embryo and system development’ and ‘multicellular organismal development’ in biological processes. By contrast, the downregulated genes were involved in ‘gene expression’ (GO: 0010476; P=1.81x10‑6), ‘nitrogen compound metabolic process’, ‘kidney development’ and the ‘cellular nitrogen compound metabolic process’. These differentially expressed lncRNAs could be classified into four classes, namely, the enhancer lncRNA nearby coding gene, HOX cluster, long‑intergenic non‑coding RNAs (lincRNAs) nearby coding gene and Rinn lincRNAs. Coding‑non‑coding gene co‑expression network analysis showed the interregulation of lncRNAs and mRNAs in OC development. In conclusion, dysregulated lncRNA and mRNA expression could promote OC development. Further study may validate a number as OC markers and provide novel insights into ovarian cancer biology.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

View References

1 

Manchanda R and Menon U: Setting the threshold for surgical prevention in women at increased risk of ovarian cancer. Int J Gynecol Cancer. 28:34–42. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, et al: Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): Overall survival results of a phase 3 randomised trial. Lancet Oncol. 16:928–936. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Prat J: Ovarian carcinomas: Five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 460:237–249. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Schuijer M and Berns EM: TP53 and ovarian cancer. Hum Mutat. 21:285–291. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Balch C, Fang F, Matei DE, Huang TH and Nephew KP: Minireview: Epigenetic changes in ovarian cancer. Endocrinology. 150:4003–4011. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Eddy SR: Non-coding RNA genes and the modern RNA world. Nat Rev Genet. 2:919–929. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Wilusz JE, Sunwoo H and Spector DL: Long noncoding RNAs: Functional surprises from the RNA world. Genes Dev. 23:1494–1504. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al: Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 458:223–227. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Mattick JS: The genetic signatures of noncoding RNAs. PLoS Genet. 5:e10004592009. View Article : Google Scholar : PubMed/NCBI

11 

Geretto M, Pulliero A, Rosano C, Zhabayeva D, Bersimbaev R and Izzotti A: Resistance to cancer chemotherapeutic drugs is determined by pivotal microRNA regulators. Am J Cancer Res. 7:1350–1371. 2017.PubMed/NCBI

12 

Lu YM, Shang C, Ou YL, Yin D, Li YN, Li X, Wang N and Zhang SL: miR-200c modulates ovarian cancer cell metastasis potential by targeting zinc finger E-box-binding homeobox 2 (ZEB2) expression. Med Oncol. 31:1342014. View Article : Google Scholar : PubMed/NCBI

13 

Guttman M and Rinn JL: Modular regulatory principles of large non-coding RNAs. Nature. 482:339–346. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Wapinski O and Chang HY: Long noncoding RNAs and human disease. Trends Cell Biol. 21:354–361. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Gutschner T and Diederichs S: The hallmarks of cancer: A long non-coding RNA point of view. RNA Biol. 9:703–719. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Gibb EA, Vucic EA, Enfield KS, Stewart GL, Lonergan KM, Kennett JY, Becker-Santos DD, MacAulay CE, Lam S, Brown CJ and Lam WL: Human cancer long non-coding RNA transcriptomes. PLoS One. 6:e259152011. View Article : Google Scholar : PubMed/NCBI

17 

Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F and Zheng SS: Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 18:1243–1250. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Qiu JJ, Lin YY, Ye LC, Ding JX, Feng WW, Jin HY, Zhang Y, Li Q and Hua KQ: Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer. Gynecol Oncol. 134:121–128. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, Tanaka F, Shibata K, Suzuki A, Komune S, et al: Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 71:6320–6326. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Szafron LM, Balcerak A, Grzybowska EA, Pienkowska-Grela B, Podgorska A, Zub R, Olbryt M, Pamula-Pilat J, Lisowska KM, Grzybowska E, et al: The putative oncogene, CRNDE, is a negative prognostic factor in ovarian cancer patients. Oncotarget. 6:43897–43910. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Barber HR, Sommers SC, Synder R and Kwon TH: Histologic and nuclear grading and stromal reactions as indices for prognosis in ovarian cancer. Am J Obstet Gynecol. 121:795–807. 1975.PubMed/NCBI

23 

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E and Chang HY: Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 129:1311–1323. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Qin LX, Beyer RP, Hudson FN, Linford NJ, Morris DE and Kerr KF: Evaluation of methods for oligonucleotide array data via quantitative real-time PCR. BMC Bioinformatics. 7:232006. View Article : Google Scholar : PubMed/NCBI

27 

Bhan A, Soleimani M and Mandal SS: Long noncoding RNA and cancer: A new paradigm. Cancer Res. 77:3965–3981. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Chen S, Wu DD, Sang XB, Wang LL, Zong ZH, Sun KX, Liu BL and Zhao Y: The lncRNA HULC functions as an oncogene by targeting ATG7 and ITGB1 in epithelial ovarian carcinoma. Cell Death Dis. 8:e31182017. View Article : Google Scholar : PubMed/NCBI

29 

Fu X, Zhang L, Dan L, Wang K and Xu Y: LncRNA EWSAT1 promotes ovarian cancer progression through targeting miR-330-5p expression. Am J Transl Res. 9:4094–4103. 2017.PubMed/NCBI

30 

Yu J, Han Q and Cui Y: Decreased long non-coding RNA SPRY4-IT1 contributes to ovarian cancer cell metastasis partly via affecting epithelial-mesenchymal transition. Tumour Biol. 39:10104283177091292017. View Article : Google Scholar : PubMed/NCBI

31 

Zhu FF, Zheng FY, Wang HO, Zheng JJ and Zhang Q: Downregulation of lncRNA TUBA4B is associated with poor prognosis for epithelial ovarian cancer. Pathol Oncol Res. 24:419–425. 2018. View Article : Google Scholar : PubMed/NCBI

32 

Guo L, Peng Y, Meng Y, Liu Y, Yang S, Jin H and Li Q: Expression profiles analysis reveals an integrated miRNA-lncRNA signature to predict survival in ovarian cancer patients with wild-type BRCA1/2. Oncotarget. 8:68483–68492. 2017.PubMed/NCBI

33 

Wang L, Hu Y, Xiang X, Qu K and Teng Y: Identification of long non-coding RNA signature for paclitaxel-resistant patients with advanced ovarian cancer. Oncotarget. 8:64191–64202. 2017.PubMed/NCBI

34 

Cao Y, Shi H, Ren F, Jia Y and Zhang R: Long non-coding RNA CCAT1 promotes metastasis and poor prognosis in epithelial ovarian cancer. Exp Cell Res. 359:185–194. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Shen L, Liu W, Cui J, Li J and Li C: Analysis of long non-coding RNA expression profiles in ovarian cancer. Oncol Lett. 14:1526–1530. 2017. View Article : Google Scholar : PubMed/NCBI

36 

Ding Y, Yang DZ, Zhai YN, Xue K, Xu F, Gu XY and Wang SM: Microarray expression profiling of long non-coding RNAs in epithelial ovarian cancer. Oncol Lett. 14:2523–2530. 2017. View Article : Google Scholar : PubMed/NCBI

37 

Kaur P, Tan JR, Karolina DS, Sepramaniam S, Armugam A, Wong PT and Jeyaseelan K: A long non-coding RNA, BC048612 and a microRNA, miR-203 coordinate the gene expression of neuronal growth regulator 1 (NEGR1) adhesion protein. Biochim Biophys Acta. 1863:533–543. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Ji J, Tang J, Deng L, Xie Y, Jiang R, Li G and Sun B: LINC00152 promotes proliferation in hepatocellular carcinoma by targeting EpCAM via the mTOR signaling pathway. Oncotarget. 6:42813–42824. 2015. View Article : Google Scholar : PubMed/NCBI

39 

Chen H, Du G, Song X and Li L: Non-coding transcripts from enhancers: New insights into enhancer activity and gene expression regulation. Genomics Proteomics Bioinformatics. 15:201–207. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lu YM, Wang Y, Liu SQ, Zhou MY and Guo YR: Profile and validation of dysregulated long non‑coding RNAs and mRNAs in ovarian cancer. Oncol Rep 40: 2964-2976, 2018.
APA
Lu, Y., Wang, Y., Liu, S., Zhou, M., & Guo, Y. (2018). Profile and validation of dysregulated long non‑coding RNAs and mRNAs in ovarian cancer. Oncology Reports, 40, 2964-2976. https://doi.org/10.3892/or.2018.6654
MLA
Lu, Y., Wang, Y., Liu, S., Zhou, M., Guo, Y."Profile and validation of dysregulated long non‑coding RNAs and mRNAs in ovarian cancer". Oncology Reports 40.5 (2018): 2964-2976.
Chicago
Lu, Y., Wang, Y., Liu, S., Zhou, M., Guo, Y."Profile and validation of dysregulated long non‑coding RNAs and mRNAs in ovarian cancer". Oncology Reports 40, no. 5 (2018): 2964-2976. https://doi.org/10.3892/or.2018.6654
Copy and paste a formatted citation
x
Spandidos Publications style
Lu YM, Wang Y, Liu SQ, Zhou MY and Guo YR: Profile and validation of dysregulated long non‑coding RNAs and mRNAs in ovarian cancer. Oncol Rep 40: 2964-2976, 2018.
APA
Lu, Y., Wang, Y., Liu, S., Zhou, M., & Guo, Y. (2018). Profile and validation of dysregulated long non‑coding RNAs and mRNAs in ovarian cancer. Oncology Reports, 40, 2964-2976. https://doi.org/10.3892/or.2018.6654
MLA
Lu, Y., Wang, Y., Liu, S., Zhou, M., Guo, Y."Profile and validation of dysregulated long non‑coding RNAs and mRNAs in ovarian cancer". Oncology Reports 40.5 (2018): 2964-2976.
Chicago
Lu, Y., Wang, Y., Liu, S., Zhou, M., Guo, Y."Profile and validation of dysregulated long non‑coding RNAs and mRNAs in ovarian cancer". Oncology Reports 40, no. 5 (2018): 2964-2976. https://doi.org/10.3892/or.2018.6654
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team