Prognostic Value of RNASEH2A-, CDK1-, and CD151-Related Pathway Gene Profiling for Kidney Cancers.

The nucleotide degrading enzyme gene <italic>RNASEH2A</italic> (ribonuclease H2 subunit A) has been found to be overexpressed in cancers. Our aim was to understand the role of <italic>RNASEH2A</italic> in cancer prognostication and to establish a scoring system based on the expressions of genes interacting with <italic>RNASEH2A.</italic> We screened the nucleotide degrading enzyme gene expression in RNAseq data of 14 cancer types derived from The Cancer Genome Atlas (TCGA) and found that <italic>RNASEH2A</italic> overexpression was associated with poor patient survival only in renal cell carcinomas (RCCs). Further cluster analyses of samples with poor outcomes revealed that cluster of differentiation 151 (<italic>CD151</italic>) upregulation correlated with low cyclin dependent kinase 1 (<italic>CDK1</italic>) and high <italic>RNASEH2A</italic> expression. The combination of low <italic>CD151</italic> expression and high <italic>RNASEH2A</italic> expression resulted in impaired proliferation in four kidney cancer cell lines, suggesting potential synthetic dosage lethality (SDL) interactions between the two genes. A prognostication scoring system was established based on the expression levels of <italic>RNASEH2A-</italic>, <italic>CDK1-</italic>, and <italic>CD151-</italic>related genes, which could effectively predict the overall survival in a TCGA clear cell RCC cohort (<italic>n</italic> = 533, 995.3 versus 2242.2 days, <italic>p</italic> < 0.0001), in another clear cell renal cell carcinoma (ccRCC) cohort E-GEOD-22541 (<italic>n</italic> = 44, 390.0 versus 1889.2 days, <italic>p</italic> = 0.0007), and in a TCGA papillary RCC (pRCC) cohort (<italic>n</italic> = 287, 741.6 versus 1623.7 days, <italic>p</italic> < 0.0001). Our results provide a clinically applicable prognostication scoring system for renal cancers. [ABSTRACT FROM AUTHOR]