Identification of CXCL10 as a Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

Abstract

BackgroundOne of the widespread forms of kidney tumor is clear cell renal cell carcinoma (ccRCC), with poor prognosis and insensitivity to radio chemotherapy as there is limited capacity to understand the disease mechanism. This study aims at identifying potential biomarkers and the underlying processes of ccRCC using bioinformatics analysis.MethodsTranscriptome data of relevant samples were downloaded from The Cancer Genome Atlas (TCGA) database. R software was used to screen differentially expressed genes (DEGs) using the “edgeR” package. Two types of analysis—Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment—were accomplished by applying Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Search Tool for the Retrieval of Interacting Genes database (STRING) online bioinformatics tools. A protein–protein interaction (PPI) network of the identified DEGs was constructed using Cytoscape software, and hub genes were subsequently selected via the Cytohubba plug-in. The selected genes were input into Oncomine for verification. Finally, selected hub genes were analyzed by doing survival analysis to notice the relationship between survival (OS) rate and the selected genes’ level of expression.ResultsThere were 1,855 DEGs found connected to ccRCC, with 1,207 upregulated genes and 648 downregulated genes. G-protein-coupled receptor signaling pathway, integral component of membrane, calcium ion binding, and cytokine–cytokine receptor interaction were among the DEGs discovered. Oncomine confirmed the top six hub genes from the PPI network (C3, CXCR3, CXCL10, CCR5, CCL4, and CCL5). A high level of expression of CXCL10, one of these hub genes, was linked to a poor prognosis in individuals with ccRCC. The results of survival analysis showed that the expression level of CXCL10 was significantly correlated with the prognosis of ccRCC patients (p < 0.05).ConclusionsFrom the analysis, the following results were drawn: CXCL10 might be a potential prognostic biomarker and novel therapeutic target for ccRCC.

Clear Cell Renal Cell Carcinoma: A Comprehensive in silico Study in Searching for Therapeutic Targets

“…The 12 hub genes were identified as essential genes in the pathogenesis of ccRCC. Notably, some of the identified hub genes in the present study were previously recognized as key players in the pathogenesis of ccRCC [35–39]. A brief description of the identified hub genes is provided in online supplementary file 2.…”

Predictive value of CXCL10 for the occurrence of immune‐related adverse events in patient with renal cell carcinoma

“…RCC exhibits prominent characteristics of inflammation. Serum CXCL10 levels were shown to be higher in patients with RCC than healthy controls, 25 due in part to tumor‐intrinsic CXCL10 expression 26 . Given that these observations raise the possibility that the nature of RCC itself may affect the development of irAEs, we measured the levels of CXCL10 in RCC tissues.…”

“…Serum CXCL10 levels were shown to be higher in patients with RCC than healthy controls, 25 due in part to tumor-intrinsic CXCL10 expression. 26 Given that these observations raise the possibility that the nature of RCC itself may affect the development of irAEs, we measured the levels of CXCL10 in RCC tissues. However, no correlation was observed between CXCL10 expression in tumor tissues and plasma CXCL10 levels in the present study, suggesting that tumor-derived CXCL10 is not responsible for irAEassociated high CXCL10 levels.…”

Renal Cell Carcinoma: A Comprehensive in Silico Study in Searching for Therapeutic Targets

“…Notably, some of the identi ed hub genes in the present study were previously recognized as key players in the pathogenesis of ccRCC [24][25][26][27][28]. A brief description of the identi ed hub genes is provided in supplementary le 2.…”