Abstract
BackgroundClear cell renal cell carcinoma (ccRCC) is a common genitourinary cancer type with a high mortality rate. Due to a diverse range of biochemical alterations and a high level of tumor heterogeneity, it is crucial to select highly validated prognostic biomarkers to be able to identify subtypes of ccRCC early and apply precision medicine approaches.MethodsTranscriptome data of ccRCC and clinical traits of patients were obtained from the GSE126964 dataset of Gene Expression Omnibus and The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) database. Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) screening were applied to detect common differentially co-expressed genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, survival analysis, prognostic model establishment, and gene set enrichment analysis were also performed. Immunohistochemical analysis results of the expression levels of prognostic genes were obtained from The Human Protein Atlas. Single-gene RNA sequencing data were obtained from the GSE131685 and GSE171306 datasets.ResultsIn the present study, a total of 2,492 DEGs identified between ccRCC and healthy controls were filtered, revealing 1,300 upregulated genes and 1,192 downregulated genes. Using WGCNA, the turquoise module was identified to be closely associated with ccRCC. Hub genes were identified using the maximal clique centrality algorithm. After having intersected the hub genes and the DEGs in GSE126964 and TCGA-KIRC dataset, and after performing univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses, ALDOB, EFHD1, and ESRRG were identified as significant prognostic factors in patients diagnosed with ccRCC. Single-gene RNA sequencing analysis revealed the expression profile of ALDOB, EFHD1, and ESRRG in different cell types of ccRCC.ConclusionsThe present results demonstrated that ALDOB, EFHD1, and ESRRG may act as potential targets for medical therapy and could serve as diagnostic biomarkers for ccRCC.
Highlights
Renal cell carcinoma (RCC) is one of the most common genitourinary cancer types worldwide, and it has a number of heterogeneous histological subtypes, with clear cell RCC accounting for ~85% of all cases [1]
Using Weighted gene coexpression network analysis (WGCNA), the turquoise module was identified to be closely associated with clear cell RCC (ccRCC)
After having intersected the hub genes and the differentially expressed gene (DEG) in GSE126964 and TCGA-KIRC dataset, and after performing univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses, ALDOB, EFHD1, and ESRRG were identified as significant prognostic factors in patients diagnosed with ccRCC
Summary
Renal cell carcinoma (RCC) is one of the most common genitourinary cancer types worldwide, and it has a number of heterogeneous histological subtypes, with clear cell RCC (ccRCC) accounting for ~85% of all cases [1]. Due to diverse biochemical alterations and a high level of tumor heterogeneity, it is important to select highly validated prognostic biomarkers to identify subtypes of ccRCC early and apply precision medicine approaches [6]. A loss-of-function mutation in the VHL gene induces the aberrant regulation of a number of VHL-mediated targets, pathways, and processes, which is a significant step in the development of ccRCC [10, 11]. Due to a diverse range of biochemical alterations and a high level of tumor heterogeneity, it is crucial to select highly validated prognostic biomarkers to be able to identify subtypes of ccRCC early and apply precision medicine approaches
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