Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer
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 marker...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13048-020-00632-9 |
| _version_ | 1797972371664011264 |
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| author | Guanghui Gong Ting Lin Yishu Yuan |
| author_facet | Guanghui Gong Ting Lin Yishu Yuan |
| author_sort | Guanghui Gong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T03:47:28Z |
| format | Article |
| id | doaj.art-48bba044ce1f4b149deea038a3e773ab |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-11T03:47:28Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-48bba044ce1f4b149deea038a3e773ab2023-01-02T02:28:19ZengBMCJournal of Ovarian Research1757-22152020-03-0113111010.1186/s13048-020-00632-9Integrated analysis of gene expression and DNA methylation profiles in ovarian cancerGuanghui Gong0Ting Lin1Yishu Yuan2Department of Pathology, Xiangya Hospital, Central South UniversityHunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese MedicineDepartment of Pathology, Xiangya Hospital, Central South UniversityAbstract 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.http://link.springer.com/article/10.1186/s13048-020-00632-9Ovarian cancerMethylationGene expression |
| spellingShingle | Guanghui Gong Ting Lin Yishu Yuan Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer Journal of Ovarian Research Ovarian cancer Methylation Gene expression |
| title | Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer |
| title_full | Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer |
| title_fullStr | Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer |
| title_full_unstemmed | Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer |
| title_short | Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer |
| title_sort | integrated analysis of gene expression and dna methylation profiles in ovarian cancer |
| topic | Ovarian cancer Methylation Gene expression |
| url | http://link.springer.com/article/10.1186/s13048-020-00632-9 |
| work_keys_str_mv | AT guanghuigong integratedanalysisofgeneexpressionanddnamethylationprofilesinovariancancer AT tinglin integratedanalysisofgeneexpressionanddnamethylationprofilesinovariancancer AT yishuyuan integratedanalysisofgeneexpressionanddnamethylationprofilesinovariancancer |