Stemness-associated senescence genes as potential novel risk factors for papillary renal cell carcinoma

Transl Androl Urol. 2021 Nov;10(11):4241-4252. doi: 10.21037/tau-21-913.

Abstract

Background: Papillary renal cell carcinoma (PRCC) is the 2nd most common type of renal carcinoma; however, there is limited data about PRCC, and strategies for the diagnosis and treatment of PRCC need to be identified.

Methods: In this study, the stemness-associated senescence (SAS) phenotype of PRCC was obtained by a bioinformatics analysis. We acquired the gene expression profiles of patients with PRCC and calculated the PRCC messenger ribonucleic acid stemness index (mRNAsi). We then screened the SAS genes from the GenAge database. A least absolute shrinkage and selection operator-Cox regression was conducted to examine correlations between risk signatures and the abundance of the SAS genes in the PRCC samples. Functional enrichment analyses were then performed via molecular co-expression studies of mRNAsi, and the risk scores of PRCC patients were calculated.

Results: We identified the following 8 SAS signatures that were strongly associated with prognosis in PRCC patients: cyclin-dependent kinase 1, heat shock protein family D member 1, platelet-derived growth factor receptor A, cyclin-dependent kinase inhibitor 2B, pyrroline-5-carboxylate reductase 1, sequestosome-1, sirtuin-3, and cyclin-dependent kinase inhibitor 1A. The SAS signatures were significantly associated with the stage and type of PRCC. The calculated risk scores can be used to divide PRCC patients into low- and high-risk groups, and provide guidance in determining treatment plans.

Conclusions: We have developed a reliable prognostic tool to predict the clinical outcomes of PRCC patients. This tool could improve treatment decisions regarding drug therapy, surgery, and conservative options.

Keywords: Papillary renal cell carcinoma (PRCC); mRNA stemness index; prognostic value; risk score; stemness-associated senescence signatures.