Integrated Analysis of Gene Expression and DNA Methylation Profiles in Ovarian Cancer

Overview

Journal J Ovarian Res

Publisher Biomed Central

Specialties Gynecology & Obstetrics
Reproductive Medicine

Date 2020 Mar 21

PMID 32192517

Citations 25

Authors

Guanghui Gong

Ting Lin

Yishu Yuan

Affiliations

Soon will be listed here.

Abstract

Background: Ovarian cancer is an epithelial malignancy that intrigues people for its poor outcome and lack of efficient treatment, while methylation is an important mechanism that have been recognized in many malignancies. In this study, we attempt to assess abnormally methylated gene markers and pathways in ovarian cancer by integrating three microarray datasets.

Methods: Three datasets including expression (GSE26712 and GSE66957) and methylation (GSE81224) datasets were accessed. GEO2R platform was used to detect abnormally methylated-differentially expressed genes. Protein-protein interaction (PPI) networks were built and analysed for hypermethylated and hypermethylated differentially expressed genes using Cytoscape software and Mcode app. GEPIA and cBioPortal platforms were used to validate the expression of the hub genes and the correlation between their mRNA expressions and methylation levels. Kaplan Meier-plotter platform were used to assess the prognostic significance of the hub genes.

Results: Six hundred eighty-one hypomethylated-upregulated genes were detected and involved in Rap1 signaling pathway, biosynthesis of amino acids, endocrine resistance, apoptosis, pathways in cancer. The hub genes were TNF, UBC, SRC, ESR1, CDK1, PECAM1, CXCR4, MUC1, IKBKG. Additionally, 337 hypermethylated-downregulated genes were detected and involved in pathways in cancer, focal adhesion, sphingolipid signaling pathway, EGFR tyrosine kinase inhibitor resistance, cellular senescence. The hub genes were BDNF, CDC42, CD44, PPP2R5C, PTEN, UBB, BMP2, FOXO1, KLHL2. TNF, ESR1, MUC1, CD44, PPP2R5C, PTEN, UBB and FOXO1 showed significant negative correlation between their mRNA expressions and methylation levels. TNF, ESR1 and FOXO1 showed prognostic significance.

Conclusions: Two novel gene networks were found for ovarian cancer. TNF, ESR1, MUC1 and FOXO1 are our candidate genes that might take part in ovarian cancer progression in an epigenetic approach, TNF, ESR1 and FOXO1 may serve as potential markers for ovarian cancer prognosis evaluation.

Citing Articles

Epigenetic Modulation of Estrogen Receptor Signaling in Ovarian Cancer.

Skrzypczak M, Wolinska E, Adaszek L, Ortmann O, Treeck O Int J Mol Sci. 2025; 26(1.

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CpG hypomethylation at proximal promoter and 5'UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancer.

Li J, Mei B, Zhu Y, Huang J, Li M, Wang D Sci Rep. 2024; 14(1):30945.

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USP5 Stabilizes IKBKG Through Deubiquitination to Suppress Ferroptosis and Promote Growth in Non-small Cell Lung Cancer.

Li Y, Qiu G, Zhou M, Chen Q, Liao X Cell Biochem Biophys. 2024; .

PMID: 39397222 DOI: 10.1007/s12013-024-01574-5.

Recognition of differently expressed genes and DNA methylation markers in patients with Lupus nephritis.

Liu Z, Liu F, Xie J, Zhao Z, Pan S, Liu D J Transl Int Med. 2024; 12(4):367-383.

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Ovarian cancer: Diagnosis and treatment strategies (Review).

Li X, Li Z, Ma H, Li X, Zhai H, Li X Oncol Lett. 2024; 28(3):441.

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