Identification of novel gene-based risk score for prognosis in prostate cancer

Abstract

Abstract Tumor carcinogenesis and progression result from multiple genetic alterations in tumor cells. However, reliable biomarkers for prostate cancer classification remain limited, often leading to either overtreatment or inadequate treatment. Additionally, effective biomarkers for selecting patients who may benefit from immunotherapy are still lacking. Using data from TCGA-PRAD, we established gene selection criteria to develop a gene-based risk score. We identified a novel gene risk panel comprising six genes (SSTR1, CA14, HJURP, KRTAP5-1, VGF, and COMP) for prostate cancer risk classification. Patients in the high-risk group were associated with poor prognosis. The gene panel exhibited significantly enhanced predictive accuracy for progression-free survival compared to conventional clinicopathological parameters, including T stage, N stage, primary Gleason score, and secondary Gleason score. High-risk patients exhibited a higher tumor mutation burden. Notably, immune activity of CD8 + T cells, NK cells, and the type II IFN response was significantly lower in the high-risk group, indicating a more immunosuppressive environment. Furthermore, a nomogram combining the gene-based risk score with T stage and histological grade was constructed. The expression of genes in the gene-based risk score was further validated using clinical samples, and VGF was found to play a significant role in prostate cancer progression. The nomogram could serve as a valuable biomarker for distinguishing between high-risk and low-risk of PFS prostate cancer patients and for selecting patients who might benefit from immunotherapy.