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Open AccessArticle

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

1
Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan; #2 Yude Road, Taichung 40447, Taiwan
2
Division of General Pediatrics, China Medical University Children’s Hospital, Taichung 40447, Taiwan
3
College of Medicine, China Medical University, Taichung 40402, Taiwan
4
Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(6), 1586; https://doi.org/10.3390/ijms19061586
Received: 17 April 2018 / Revised: 17 May 2018 / Accepted: 22 May 2018 / Published: 28 May 2018
(This article belongs to the Collection Precision Medicine—From Bench to Bedside)
The nucleotide degrading enzyme gene RNASEH2A (ribonuclease H2 subunit A) has been found to be overexpressed in cancers. Our aim was to understand the role of RNASEH2A in cancer prognostication and to establish a scoring system based on the expressions of genes interacting with RNASEH2A. 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 RNASEH2A 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 (CD151) upregulation correlated with low cyclin dependent kinase 1 (CDK1) and high RNASEH2A expression. The combination of low CD151 expression and high RNASEH2A 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 RNASEH2A-, CDK1-, and CD151-related genes, which could effectively predict the overall survival in a TCGA clear cell RCC cohort (n = 533, 995.3 versus 2242.2 days, p < 0.0001), in another clear cell renal cell carcinoma (ccRCC) cohort E-GEOD-22541 (n = 44, 390.0 versus 1889.2 days, p = 0.0007), and in a TCGA papillary RCC (pRCC) cohort (n = 287, 741.6 versus 1623.7 days, p < 0.0001). Our results provide a clinically applicable prognostication scoring system for renal cancers. View Full-Text
Keywords: RNASEH2A; CDK1; CD151; synthetic dosage lethality; renal cell carcinoma RNASEH2A; CDK1; CD151; synthetic dosage lethality; renal cell carcinoma
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Yang, C.-A.; Huang, H.-Y.; Yen, J.-C.; Chang, J.-G. Prognostic Value of RNASEH2A-, CDK1-, and CD151-Related Pathway Gene Profiling for Kidney Cancers. Int. J. Mol. Sci. 2018, 19, 1586.

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