Development and validation of a kinase-related gene signature as a novel diagnostic and prognostic model for prostate cancer

Abstract

Background

Prostate cancer (PCa) is a prevalent malignant tumor in men worldwide. Kinases play a key role in the development of multiple tumors. Nevertheless, the role of kinases in PCa remains largely unclear.

Methods

A kinase-related gene signature was constructed by LASSO Cox regression analysis using the TCGA_PRAD cohort. The diagnostic and prognostic values of the signature were then evaulated. Furthermore, a loss-of-function assay was carried out to explore the function of NEK5 in PCa.

Results

A signature of 13 kinase-related genes (NEK5, FRK, STK39, STYK1, IGF1R, RPS6KC1, TTK, CDK1, NEK2, PTK6, DAPK1, MELK and EPHA10) was constructed. The PCa patients presenting a high-risk score according to the signature demonstrated poorer disease-free survival compared to those with a low score. Additionally, TMB was found to be remarkably increased in patients categorized as high-risk relative to low-risk patients. Moreover, the 13-gene signature may also have good predictive value for PCa diagnosis. Furthermore, NEK5 expression was remarkably elevated in PCa tissues relative to benign tissues. NEK5 deficiency significantly inhibited PCa cell growth and suppressed mitochondrial OXPHOS.

Conclusion

The 13-gene signature constructed in this study may exhibit good performance in PCa diagnosis and prognosis evaluation. We identified the oncogenic role of NEK5 in PCa. NEK5 may serve as a therapeutic target for treatting PCa.