Prognostic Values of Gene Copy Number Alterations in Prostate Cancer

Whilst risk prediction for individual prostate cancer (PCa) cases is of a high priority, the current risk stratification indices for PCa management have severe limitations. This study aimed to identify gene copy number alterations (CNAs) with prognostic values and to determine if any combination of gene CNAs could have risk stratification potentials. Clinical and genomic data of 500 PCa cases from the Cancer Genome Atlas stable were retrieved from the Genomic Data Commons and cBioPortal databases. The CNA statuses of a total of 52 genetic markers, including 21 novel markers and 31 previously identified potential prognostic markers, were tested for prognostic significance. The CNA statuses of a total of 51/52 genetic markers were significantly associated with advanced disease at an odds ratio threshold of =1.5 or =0.667. Moreover, a Kaplan-Meier test identified 27/52 marker CNAs which correlated with disease progression. A Cox Regression analysis showed that the amplification of MIR602 and deletions of MIR602, ZNF267, MROH1, PARP8, and HCN1 correlated with a progression-free survival independent of the disease stage and Gleason prognostic group grade. Furthermore, a binary logistic regression analysis identified twenty-two panels of markers with risk stratification potentials. The best model of 7/52 genetic CNAs, which included the SPOP alteration, SPP1 alteration, CCND1 amplification, PTEN deletion, CDKN1B deletion, PARP8 deletion, and NKX3.1 deletion, stratified the PCa cases into a localised and advanced disease with an accuracy of 70.0%, sensitivity of 85.4%, specificity of 44.9%, positive predictive value of 71.67%, and negative predictive value of 65.35%. This study validated prognostic gene level CNAs identified in previous studies, as well as identified new genetic markers with CNAs that could potentially impact risk stratification in PCa.

Automated summary

This study aimed to identify gene copy number alterations (CNAs) with prognostic values and determine their potential for risk stratification in prostate cancer (PCa) cases. It found that the CNA statuses of 51/52 genetic markers were significantly associated with advanced disease, and 27/52 marker CNAs correlated with disease progression. Several genetic markers, including MIR602, ZNF267, MROH1, PARP8, and HCN1, were shown to be independent prognostic factors. The best model, consisting of 7/52 genetic CNAs, accurately stratified PCa cases into localized and advanced disease with high sensitivity and moderate specificity.