Overexpression of PKMYT1 Facilitates Tumor Development and Is Correlated with Poor Prognosis in Clear Cell Renal Cell Carcinoma.

BACKGROUND Protein kinase membrane-associated tyrosine/threonine (PKMYT1) has been found in many tumors, but its association with clear cell renal cell carcinoma (ccRCC) remains unclear. MATERIAL AND METHODS PKMYT1 expression in ccRCC was examined in the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Tumor Immune Estimation Resource databases. The correlation between PKMYT1 expression and clinicopathological parameters was explored via the chi-square test. Receiver operating characteristic curves were used to estimate the diagnostic performance of PKMYT1. Kaplan-Meier curves, a Cox model, nomogram, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA) were used to evaluate the prognostic value and clinical utility of PKMYT1. Genes coexpressed with PKMYT1 in ccRCC were identified based on TCGA, the gene expression profiling interactive, and cBioPortal. Gene Set Enrichment Analysis revealed biological pathways associated with PKMYT1 in ccRCC. RESULTS Weighted gene coexpression network analysis identified PKMYT1 as one of the genes most significantly correlated with progression of histological grade. PKMYT1 was significantly upregulated in ccRCC compared with normal tissue (P<0.001), with a trend toward differentiating between individuals with ccRCC and those who were healthy (area under the curve=0.942). High PKMYT1 expression was correlated with unsatisfactory survival (hazard ratio=1.67, P=0.001), indicating that it is a risk factor for ccRCC. A nomogram incorporating PKMYT1 level was created and showed a clinical net benefit. PKMYT1 was strongly positively correlated with the anti-silencing function of 1B histone chaperone (ASF1B) gene in ccRCC. CONCLUSIONS PKMYT1 is upregulated in ccRCC and its presence indicates poor prognosis, making it a potential therapeutic target for ccRCC.