Elevated THBS3 predicts poor overall survival for clear cell renal cell carcinoma and identifies LncRNA/RBP/THBS3 mRNA networks.

ABSTRACT

This study was used to assess THBS3's overall survival (OS) prognostic values in clear cell renal cell carcinoma (ccRCC) as well as to determine the LncRNA/RNA binding protein (RBP)/THBS3 interactions. Clinical data and RNA sequencing data were gathered from the TCGA dataset. Significant pathways associated with THBS3 were identified by gene set enrichment analysis (GSEA). Cox regression analyses, both univariate and multivariate, were applied to assess factors with independent prognostic abilities. We also discussed THBS3's relationship to immunity. We discovered that THBS3 expression was increased in ccRCC samples, as well as shorter OS in the TCGA dataset (P<0.05). External verification results in GSE6344, ICGC, ArrayExpress, UALCAN datasets, and qRT-PCR remained consistent (all P<0.05). Cox regression analyses, both univariate and multivariate, identified THBS3 as a factor with independent prognostic ability (both P<0.001). THBS3 expression as well as several clinicopathological variables were included in the nomogram OS prognosis prediction method as well. GSEA identified four THBS3-related signal pathways and THBS3 was revealed to be significantly associated with MSI, TMB, neoantigen, and immunity (all P<0.05). We also identified several LncRNA/RBP/THBS3 mRNA networks as potentially THBS3-related mechanisms. For THBS3-related drug sensitivities, THBS3 was negatively associated with Actinomycin D, Cobimetinib, Eribulin mesilate, Geldanamycin analog, and Vinblastine, while it was positively related to Erlotinib drug sensitivity. In addition to being an independent prognostic factor for ccRCC, THBS3 had a close connection to immunity, with identifying LncRNA/RBPs/THBS3 mRNA networks. Verifications of our findings in vivo and in vitro should be done in the future.