Skip to main content

Advertisement

Log in

Decoding methylation patterns in ovarian cancer using publicly available Next-Gen sequencing data

  • Original Article
  • Published:
Network Modeling Analysis in Health Informatics and Bioinformatics Aims and scope Submit manuscript

Abstract

Ovarian cancer (OC), one of the most frequent forms of cancer among women all over the world, inflicts a substantial danger to the health of human beings. An in-depth comprehension of its latent processes at the molecular level is the answer to evolving successful earmarked therapies. For an effective genomic assay, deep transcriptional sequencing has been used via Next-generation sequencing tools which are beneficial in studying OC and its related counterparts. ChIP-Seq data for a malignant and benign specimen of OC underwent comparison, and identification of differential peaks were carried out based on fold change and peaks were then annotated. BioGRID was employed to perform protein-protein interaction (PPI) network analysis, which was then constructed with Cytoscape. Highly connected genes from the constructed network were then screened. Utilizing the additional data sets from other OC cell lines gave two new classes of genes for which there is no documented role in the progression of the disease. PAX2, PAX5, FOXP1 and KLF16 are some of the promising genes whose presence among differential peaks led to the positive conclusion of their role in OC. Recent literature studies of these genes are also in conformity with the findings. Potential OC-related genes identified through our findings increase the interpretation of OC and thus provide direction for conducting research in near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Bailey T, Krajewski P, Ladunga I et al (2013) Practical guidelines for the comprehensive analysis of ChIP-seq data. PLoS Comput Biol 9:e1003326

    Article  Google Scholar 

  • Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6:107–116. https://doi.org/10.1038/nrc1799

    Article  Google Scholar 

  • Bioinformatics B (2011) FastQC: a quality control tool for high throughput sequence data. Camb UK Babraham Inst

  • Bird AP, Wolffe AP (1999) Methylation-induced repression—belts, braces, and chromatin. Cell 99:451–454. https://doi.org/10.1016/S0092-8674(00)81532-9

    Article  Google Scholar 

  • Catteau A, Harris WH, Xu C-F, Solomon E (1999) Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics. Oncogene 18:1957–1965. https://doi.org/10.1038/sj.onc.1202509

    Article  Google Scholar 

  • Chen C, Sun M-Z, Liu S et al (2010) Smad4 mediates malignant behaviors of human ovarian carcinoma cell through the effect on expressions of E-cadherin, plasminogen activator inhibitor-1 and VEGF. Bmb Rep 43:554–560

    Article  Google Scholar 

  • Choi EJ, Seo EJ, Kim DK et al (2016) FOXP1 functions as an oncogene in promoting cancer stem cell-like characteristics in ovarian cancer cells. Oncotarget 7:3506

    Google Scholar 

  • Cobaleda C, Schebesta A, Delogu A, Busslinger M (2007) Pax5: the guardian of B cell identity and function. Nat Immunol 8:463

    Article  Google Scholar 

  • Costello JF, Plass C (2001) Methylation matters. J Med Genet 38:285–303

    Article  Google Scholar 

  • Darcy KM, Brady WE, Blancato JK et al (2009) Prognostic relevance of c-MYC gene amplification and polysomy for chromosome 8 in suboptimally-resected, advanced stage epithelial ovarian cancers: a gynecologic oncology Group study. Gynecol Oncol 114:472–479. https://doi.org/10.1016/j.ygyno.2009.05.012

    Article  Google Scholar 

  • Elias KM, Emori MM, Westerling T et al (2016) Epigenetic remodeling regulates transcriptional changes between ovarian cancer and benign precursors. JCI Insight 1

  • Esteller M (2008) Epigenetics in cancer. N Engl J Med 358:1148–1159. https://doi.org/10.1056/NEJMra072067

    Article  Google Scholar 

  • Esteller M, Silva JM, Dominguez G et al (2000) Promoter Hypermethylation and BRCA1 Inactivation in Sporadic Breast and Ovarian Tumors. JNCI J Natl Cancer Inst 92:564–569. https://doi.org/10.1093/jnci/92.7.564

    Article  Google Scholar 

  • Goncharenko-Khaider N, Matte I, Lane D et al (2012) Ovarian cancer ascites increase Mcl-1 expression in tumor cells through ERK1/2-Elk-1 signaling to attenuate TRAIL-induced apoptosis. Mol Cancer 11:84

    Article  Google Scholar 

  • Hein S, Mahner S, Kanowski C et al (2009) Expression of Jun and Fos proteins in ovarian tumors of different malignant potential and in ovarian cancer cell lines. Oncol Rep 22:177–183

    Google Scholar 

  • Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042–2054. https://doi.org/10.1056/NEJMra023075

    Article  Google Scholar 

  • Imoto I, Sonoda I, Yuki Y, Inazawa J (2001) Identification and characterization of human PKNOX2, a novel homeobox-containing gene. Biochem Biophys Res Commun 287:270–276

    Article  Google Scholar 

  • Jacobs I, Bast RC (1989) The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod 4:1–12. https://doi.org/10.1093/oxfordjournals.humrep.a136832

    Article  Google Scholar 

  • Jemal A, Murray T, Ward E et al (2005) Cancer Statistics, 2005. CA Cancer J Clin 55:10–30. https://doi.org/10.3322/canjclin.55.1.10

    Article  Google Scholar 

  • Johnson DS, Mortazavi A, Myers RM, Wold B (2007) Genome-wide mapping of in vivo protein-DNA interactions. Science 316:1497–1502

    Article  Google Scholar 

  • Koukoura O, Spandidos DA, Daponte A, Sifakis S (2014) DNA methylation profiles in ovarian cancer: Implication in diagnosis and therapy (Review). Mol Med Rep 10:3–9

    Article  Google Scholar 

  • Kumar H, Naik PA, Pardasani KR (2017) Finite element model to study calcium distribution in T lymphocyte involving buffers and ryanodine receptors. Proc Natl Acad Sci India Sect Phys Sci. https://doi.org/10.1007/s40010-017-0380-7

    Article  Google Scholar 

  • Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9:357

    Article  Google Scholar 

  • Lerdrup M, Johansen JV, Agrawal-Singh S, Hansen K (2016) An interactive environment for agile analysis and visualization of ChIP-sequencing data. Nat Struct Mol Biol 23:349

    Article  Google Scholar 

  • Melnikov A, Scholtens D, Godwin A, Levenson V (2009) Differential methylation profile of ovarian cancer in tissues and plasma. J Mol Diagn 11:60–65. https://doi.org/10.2353/jmoldx.2009.080072

    Article  Google Scholar 

  • Naik PA, Pardasani KR (2015) One dimensional finite element model to study calcium distribution in oocytes in presence of VGCC, RyR and Buffers. http://www.ingentaconnect.com/content/asp/jmihi/2015/00000005/00000003/art00005. Accessed 20 May 2018

  • Naik PA, Pardasani KR (2016) Finite element model to study calcium distribution in oocytes involving voltage gated Ca2 + channel, ryanodine receptor and buffers. Alex J Med 52:43–49. https://doi.org/10.1016/j.ajme.2015.02.002

    Article  Google Scholar 

  • Naik PA, Pardasani KR (2018) Three-dimensional finite element model to study effect of RyR calcium channel, ER Leak and SERCA Pump on Calcium Distribution in Oocyte Cell. Int J Comput Methods 1850091

  • Ortiz L, Aza-Blanc P, Zannini M et al (1999) The interaction between the forkhead thyroid transcription factor TTF-2 and the constitutive factor CTF/NF-1 is required for efficient hormonal regulation of the thyroperoxidase gene transcription. J Biol Chem 274:15213–15221

    Article  Google Scholar 

  • Raj U, Varadwaj PK (2017) Epigenetics and its role in human cancer. In: Translational bioinformatics and its application. Springer, pp 249–267

  • Raj U, Kumar H, Gupta S, Varadwaj PK (2016) Exploring dual inhibitors for STAT1 and STAT5 receptors utilizing virtual screening and dynamics simulation validation. J Biomol Struct Dyn 34:2115–2129. https://doi.org/10.1080/07391102.2015.1108870

    Article  Google Scholar 

  • Raj U, Aier I, Semwal R, Varadwaj PK (2017) Identification of novel dysregulated key genes in breast cancer through high throughput ChIP-Seq data analysis. Sci Rep 7:3229

    Article  Google Scholar 

  • Scardoni G, Petterlini M, Laudanna C (2009) Analyzing biological network parameters with CentiScaPe. Bioinformatics 25:2857–2859

    Article  Google Scholar 

  • Semenova EA, Kwon M, Monkhorst K et al (2016) Transcription factor NFIB is a driver of small cell lung cancer progression in mice and marks metastatic disease in patients. Cell Rep 16:631–643

    Article  Google Scholar 

  • Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504

    Article  Google Scholar 

  • Song H, Kwan S-Y, Izaguirre DI et al (2013) PAX2 expression in ovarian cancer. Int J Mol Sci 14:6090–6105

    Article  Google Scholar 

  • Tian C, Ambrosone CB, Darcy KM et al (2012) Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study. Gynecol Oncol 124:575–581. https://doi.org/10.1016/j.ygyno.2011.11.022

    Article  Google Scholar 

  • Tuefferd M, Couturier J, Penault-Llorca F et al (2007) HER2 status in ovarian carcinomas: a multicenter GINECO study of 320 patients. Plos One 2:e1138. https://doi.org/10.1371/journal.pone.0001138

    Article  Google Scholar 

  • Ushijima T, Asada K (2010) Aberrant DNA methylation in contrast with mutations. Cancer Sci 101:300–305. https://doi.org/10.1111/j.1349-7006.2009.01434.x

    Article  Google Scholar 

  • Wang J, Galvao J, Beach KM et al (2016) Novel roles and mechanism for krüppel-like factor 16 (KLF16) regulation of neurite outgrowth and ephrin receptor A5 (EphA5) expression in retinal ganglion cells. J Biol Chem 291:18084–18095

    Article  Google Scholar 

  • Weber M, Schübeler D (2007) Genomic patterns of DNA methylation: targets and function of an epigenetic mark. Curr Opin Cell Biol 19:273–280. https://doi.org/10.1016/j.ceb.2007.04.011

    Article  Google Scholar 

  • Xia Y, Chang T, Wang Y et al (2014) YAP promotes ovarian cancer cell tumorigenesis and is indicative of a poor prognosis for ovarian cancer patients. PloS One 9:e91770

    Article  Google Scholar 

  • Xu J, Zhang Y (2012) A generalized linear model for peak calling in ChIP-Seq data. J Comput Biol 19:826–838

    Article  MathSciNet  Google Scholar 

  • Yeung T-L, Leung CS, Wong K-K et al (2017) ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells. Oncotarget 8:16951

    Google Scholar 

  • Yoo CB, Jones PA (2006) Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 5:37–50. https://doi.org/10.1038/nrd1930

    Article  Google Scholar 

  • Zhang Y, Liu T, Meyer CA et al (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9:R137

    Article  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the Department of Bioinformatics and Applied Sciences, Indian Institute of Information Technology, Allahabad, for providing computing facility.

Author information

Authors and Affiliations

Authors

Contributions

P.K. and U.R. designed computational analyses. P.K. performed the ChIP-Seq data analysis and network studies. P.K., U.R., I.A. and P.K.V. analyzed the data and wrote the paper. All authors reviewed the manuscript.

Corresponding author

Correspondence to Pritish Kumar Varadwaj.

Ethics declarations

Conflict of interest

The authors declare no competing financial interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (XLSX 385 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, P., Raj, U., Aier, I. et al. Decoding methylation patterns in ovarian cancer using publicly available Next-Gen sequencing data. Netw Model Anal Health Inform Bioinforma 7, 12 (2018). https://doi.org/10.1007/s13721-018-0173-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13721-018-0173-1

Keywords

Navigation