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Identification of Key Biomarkers and Potential Molecular Mechanisms in Renal Cell Carcinoma by Bioinformatics
Feng Li1, Peiyuan Guo2, Keqin Dong2
1Department of Urology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China.
Abstract:
Renal cell carcinoma (RCC) is the most common form of kidney cancer, caused by renal epithelial cells. RCC remains to be a challenging public health problem worldwide. Metastases that are resistant to radiotherapy and chemotherapy are the major cause of death from cancer. However, the underlying molecular mechanism regulating the metastasis of RCC is poorly known. Publicly available databases of RCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using GEO2R analysis, whereas the Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by Gene Set Enrichment Analysis (GSEA) and Metascape. Protein-protein interaction (PPI) network of DEGs was analyzed by STRING online database, and Cytoscape software was used for visualizing PPI network. Survival analysis of hub genes was conducted using GEPIA online database. The expression levels of hub genes were investigated from The Human Protein Atlas online database and GEPIA online database. Finally, the comparative toxicogenomics database (CTD; http://ctdbase.org) was used to identify hub genes associated with tumor or metastasis. We identified 229 DEGs comprising 135 downregulated genes and 94 upregulated genes. Functional analysis revealed that these DEGs were associates with cell recognition, regulation of immune, negative regulation of adaptive immune response, and other functions. And these DEGs mainly related to P53 signaling pathway, cytokine-cytokine receptor interaction, Natural killer cell mediated cytotoxicity, and other pathways are involved. Ten genes were identified as hub genes through module analyses in the PPI network. Finally, survival analysis of 10 hub genes was conducted, which showed that the MMP2 (matrix metallo peptidase 2), DCN, COL4A1, CASR (calcium sensing receptor), GPR4 (G protein-coupled receptor 4), UTS2 (urotensin 2), and LDLR (low density lipoprotein receptor) genes were significant for survival. In this study, the DEGs between RCC and metastatic RCC were analyzed, which assist us in systematically understanding the pathogeny underlying metastasis of RCC. The MMP2, DCN, COL4A1, CASR, GPR4, UTS2, and LDLR genes might be used as potential targets to improve diagnosis and immunotherapy biomarkers for RCC.
Insights
This study identifies key genes involved in renal cell carcinoma (RCC) metastasis. Researchers found specific genes like MMP2 and CASR that could improve RCC diagnosis and immunotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Renal cell carcinoma (RCC) is a prevalent kidney cancer with poor prognosis due to metastasis.
- The molecular mechanisms driving RCC metastasis remain largely unknown, hindering effective treatment.
- Metastases are often resistant to conventional therapies, leading to high mortality rates.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) associated with RCC metastasis.
- To elucidate the molecular pathways and protein-protein interactions involved in RCC progression.
- To discover potential diagnostic and therapeutic biomarkers for metastatic RCC.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) database for RCC data.
- Identified DEGs using GEO2R, GO, and KEGG analyses (GSEA, Metascape).
- Analyzed protein-protein interaction networks (STRING, Cytoscape) and conducted survival analysis (GEPIA).
Main Results:
- Identified 229 DEGs (135 downregulated, 94 upregulated) between RCC and metastatic RCC.
- Functional enrichment revealed associations with immune response and cell recognition.
- Ten hub genes were identified, with MMP2, DCN, COL4A1, CASR, GPR4, UTS2, and LDLR showing significant survival correlation.
Conclusions:
- Differential gene expression analysis provides insights into RCC metastasis mechanisms.
- MMP2, DCN, COL4A1, CASR, GPR4, UTS2, and LDLR are potential biomarkers for RCC diagnosis and immunotherapy.
- Further research into these genes could lead to improved treatment strategies for metastatic RCC.
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