Identification of potential prognostic genes associated with the tumor microenvironment in chromophobe renal cell carcinoma based on weighted gene co-expression network analysis

Abstract Background Chromophobe renal cell carcinoma (ChRCC) is the third prevalent type of renal cell carcinoma(RCC), making up 5% of all RCCs. The objective of this study was to define prognostic genes associated with the tumor microenvironment (TME) of ChRCC. Methods Calculation of immune and stromal scores for ChRCC samples in the TCGA database using ESTIMATE algorithm. The differentially expressed genes (DEGs) were selected to construct co-expression modules by weighted gene co-expression network analysis(WGCNA), and hub modules were definited by calculating module-trait correlations to obtain TME-related DEGs. After that, we further analyzed the biological and molecular functions of these TME-related DEGs and evaluated their prognostic values. Finally, the online TIMER database was used to explore the infiltration of immune cells. Results 468 DEGs were identified based on stromal scores and immune scores, of which 442 were upregulated genes and 26 were down-regulated genes. Subsequently, the 122 overlapping genes were predicted from WGCNA, and considered as TME-related genes. After analyzing by Molecular Complex Detection (MCODE) plugin from Cytoscape software, Functional enrichments analysis showed that TME-related genes in primary modules were associated with immune responses or inflammatory. Consequently, six TME-relate genes (ALOX5, FGR, GRASP, HLA-DQA1, HLA-DRB1, and ROBO4) were found to be correlated with overall survival of ChRCC and immune cells infiltration. Conclusion We further analyzed the results by UALCAN databases, and combined with the IHC results of three specimens diagnosed with CHRCC, and finally found that the TME-relate ALOX5 may be a potential biomarker for the prognosis of ChRCC