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Identification of potential novel differentially-expressed genes and their role in invasion and migration in renal cell carcinoma.

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) remains one of the most common cancer types globally, and while it has been extensively studied, the molecular basis for its pathology remains incompletely understood. Herein, we profiled three previously published datasets (GSE66272, GSE100666, and GSE105261) in a single integrated analysis aimed at identifying disease-associated patterns of gene expression that may offer mechanistic insight into the drivers of this disease. We pooled expression data from 39 normal kidney samples and 39 kidney tumors, leading us to identify 310 differentially expressed genes (DEGs) that were linked to kidney cancer in all three analyzed datasets. Of these genes, 133 and 177 were up- and down-regulated, respectively, in cancer samples. We then incorporated these DEGs into a protein-protein interaction network with the STRING and Cytoscape tools, and we were able to identify signaling pathways significantly enriched for these DEGs. The relationship between DEG expression and ccRCC patient survival was further evaluated using a Kaplan-Meier approach, leading us to identify TIMP1 as an independent prognostic factor in ccRCC patients. When TIMP1 expression was disrupted in ccRCC cell lines, this impaired their migratory and invasive capabilities. In summary, we employed an integrative bioinformatics approach to identify ccRCC-related DEGs and associated signaling pathways. Together these findings offer novel insight into the mechanistic basis for ccRCC, potentially helping to identify novel therapeutic targets for the treatment of this deadly disease.

SUBMITTER: Shi SN

PROVIDER: S-EPMC7288970 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Identification of potential novel differentially-expressed genes and their role in invasion and migration in renal cell carcinoma.

Shi Shen-Nan SN Qin Xia X Wang Shuo S Wang Wen-Fu WF Zhu Yao-Feng YF Lin Yu Y Zhou Zun-Lin ZL Shi Ben-Kang BK Liu Xi-Gao XG

Aging 20200518 10

Clear cell renal cell carcinoma (ccRCC) remains one of the most common cancer types globally, and while it has been extensively studied, the molecular basis for its pathology remains incompletely understood. Herein, we profiled three previously published datasets (GSE66272, GSE100666, and GSE105261) in a single integrated analysis aimed at identifying disease-associated patterns of gene expression that may offer mechanistic insight into the drivers of this disease. We pooled expression data from ...[more]

PMID: 32420905

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Project description:BackgroundMethylation plays a key role in the aetiology and pathogenesis of prostate cancer (PCa). This study aimed to identify aberrantly methylated differentially expressed genes (DEGs) and pathways in PCa and explore the underlying mechanisms of tumourigenesis.MethodsExpression profile (GSE29079) and methylation profile (GSE76938) datasets were obtained from the Gene Expression Omnibus (GEO). We used R 3.4.4 software to assess aberrantly methylated DEGs. The Cancer Genome Atlas (TCGA) RNA sequencing and Illumina HumanMethylation450 DNA methylation data were utilized to validate screened genes. Functional enrichment analysis of the screened genes was performed, and a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Gens (STRING). The results were visualized in Cytoscape. After confirmation using TCGA, cBioPortal was used to examine alterations in genes of interest. Then, protein localization in PCa cells was observed using immunohistochemistry.ResultsOverall, 536 hypomethylated upregulated genes were identified that were enriched in biological processes such as negative regulation of transcription, osteoblast differentiation, intracellular signal transduction, and the Wnt signalling pathway. Pathway enrichment showed significant changes in factors involved in AMPK signalling, cancer, and adherens junction pathways. The hub oncogenes were AKT1, PRDM10, and FASN. Additionally, 322 hypermethylated downregulated genes were identified that demonstrated enrichment in biological processes including positive regulation of the MAPK cascade, muscle contraction, ageing, and signal transduction. Pathway analysis indicated enrichment in arrhythmogenic right ventricular cardiomyopathy (ARVC), focal adhesion, dilated cardiomyopathy, and PI3K-AKT signalling. The hub tumour suppressor gene was FLNA. Immunohistochemistry showed that AKT1, FASN, and FLNA were mainly expressed in PCa cell cytoplasm, while PRDM10 was mainly expressed in nuclei.ConclusionsOur results identify numerous novel genetic and epigenetic regulatory networks and offer molecular evidence crucial to understanding the pathogenesis of PCa. Aberrantly methylated hub genes, including AKT1, PRDM10, FASN, and FLNA, can be used as biomarkers for accurate PCa diagnosis and treatment. In conclusion, our study suggests that AKT1, PRDM10, and FASN may be tumour promoters and that FLNA may be a tumour suppressor in PCa. We hope these findings will draw more attention to these hub genes in future cancer studies.

Dataset Information

Identification of potential novel differentially-expressed genes and their role in invasion and migration in renal cell carcinoma.

Publications

Identification of potential novel differentially-expressed genes and their role in invasion and migration in renal cell carcinoma.

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