Identification and validation of HSD11B2 as a biomarker for metastasis and prognosis of clear cell renal cell carcinoma

Abstract

Background : Metastasis of clear cell renal cell carcinoma (ccRCC) is an important cause of death. The purpose of this study was to study the key gene in the process of tumor metastasis of ccRCC. Methods : Expression profiles of metastatic ccRCC and primary ccRCC were downloaded from the GEO database. Expression profiling and clinical data of ccRCC were downloaded from The Cancer Genome Atlas (TCGA) dataset. The R limma package was used to identify differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for overlapping DEGs. Verification of mRNA expression and survival analysis in the GEPIA2 database further identified the key gene. The expression of the key gene in clinical specimens was detected by quantitative real-time PCR (qRT-PCR). Univariate and multivariate cox analysis were performed to determine whether the key gene was independent prognostic factor. Gene Set Enrichment Analysis (GSEA) was used to identify HSD11B2 related signaling pathways. The correlations between the key gene and tumor immune infiltrates were investigated via TISIDB database. Results ：A total of 20 DEGs were screened from GSE22541, GSE85258, and GSE105261 datasets. Enrichment analysis indicated that the DEGs were mainly enriched in the extracellular matrix organization, collagen-containing extracellular matrix, extracellular matrix structural constituent, and protein digestion and absorption. Verification of mRN expression and survival analysis identified the key gene HSD11B2. qRT-PCR results showed A that HSD11B2 level was significantly down-regulated in ccRCC tissues compared with adjacent normal tissues. Multivariate Cox regression analysis showed that HSD11B2 expression was an independent prognostic factor for ccRCC patients. GSEA enrichment results showed that low expression of HSD11B2 could enrich cancer signaling pathways such as Nod-like receptor signaling pathway, cytoplasmic DNA sensing pathway and P53 signaling pathway. Immune analysis showed a significant correlation between HSD11B2 and tumor immune infiltrates in ccRCC. Conclusions : These findings suggest that HSD11B2 may play a key role in the metastasis of ccRCC, and HSD11B2 is correlated with prognosis and tumor immune infiltrates.