Dataset Information

Identification of methylation-driven genes related to prognosis in clear-cell renal cell carcinoma.

ABSTRACT: With the participation of the existing treatment methods, the prognosis of advanced clear-cell renal cell carcinoma (ccRCC) is poor. More evidence indicates the presence of methylation in ccRCC cancer cells, but there is a lack of studies on methylation-driven genes in ccRCC. We analyzed the open data of ccRCC in The Cancer Genome Atlas database to obtain ccRCC-related methylation-driven genes, and then carried out pathway enrichment, survival, and joint survival analyses. More important, we deeply explored the correlation between differential methylation sites and the expression of these driving genes. Finally, we screened 29 methylation-driven genes via MethylMix, of which six were significantly associated with the survival of ccRCC patients. This study demonstrated that the effect of hypermethylation or hypomethylation on prognosis is different, and the level of methylation of key methylation sites is associated with gene expression. We identified methylation-driven genes independently predicting prognosis in ccRCC, which offers theoretical support in bioinformatics for the study of methylation in ccRCC and a new perspective for the epigenetic study of ccRCC.

SUBMITTER: Wang J

PROVIDER: S-EPMC6899764 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Identification of methylation-driven genes related to prognosis in clear-cell renal cell carcinoma.

Wang Jia J Zhang Qiujing Q Zhu Qingqing Q Liu Chengxiang C Nan Xueli X Wang Fuxia F Fang Lihua L Liu Jie J Xie Chao C Fu Shuai S Song Bao B

Journal of cellular physiology 20190705 2

With the participation of the existing treatment methods, the prognosis of advanced clear-cell renal cell carcinoma (ccRCC) is poor. More evidence indicates the presence of methylation in ccRCC cancer cells, but there is a lack of studies on methylation-driven genes in ccRCC. We analyzed the open data of ccRCC in The Cancer Genome Atlas database to obtain ccRCC-related methylation-driven genes, and then carried out pathway enrichment, survival, and joint survival analyses. More important, we dee ...[more]

PMID: 31273792

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Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is a tumor that frequently shows the hematogenous pathway and tends to be resistant to radiotherapy and chemotherapy. However, the exact mechanism of ccRCC metastasis remains unknown.MethodsDifferentially expressed genes (DEGs) of three gene expression profiles (GSE85258, GSE105288 and GSE22541) downloaded from the Gene Expression Omnibus (GEO) database were analyzed by GEO2R analysis, and co-expressed DEGs among the datasets were identified using a Venn drawing tool. The co-expressed DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and hub genes were determined based on the protein-protein interaction network established by STRING. After survival analysis performed on UALCAN website, possible key genes were selected and verified in ccRCC cell lines and ccRCC tissues (n = 44). Statistical analysis was conducted using GraphPad Prism (Version 8.1.1).ResultsA total of 104 co-expressed DEGs were identified in the three datasets. Pathway analysis revealed that these genes were enriched in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption and focal adhesion. Survival analysis on 17 hub genes revealed that four key genes with a significant impact on survival: procollagen C-endopeptidase enhancer (PCOLCE), prolyl 4-hydroxylase subunit beta (P4HB), collagen type VI alpha 2 (COL6A2) and collagen type VI alpha 3 (COL6A3). Patients with higher expression of these key genes had worse survival than those with lower expression. In vitro experiments revealed that the mRNA expression levels of PCOLCE, P4HB and COL6A2 were three times higher and that of COL6A3 mRNA was 16 times higher in the metastatic ccRCC cell line Caki-1 than the corresponding primary cell line Caki-2. Immunohistochemistry revealed higher expression of the proteins encoded by these four genes in metastatic ccRCC compared with tumors from the corresponding primary sites, with statistical significance.ConclusionPCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.

Dataset Information

Identification of methylation-driven genes related to prognosis in clear-cell renal cell carcinoma.

Publications

Identification of methylation-driven genes related to prognosis in clear-cell renal cell carcinoma.

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