A new risk stratification system of prostate cancer to identify high-risk biochemical recurrence patients

BACKGROUND: Biochemical recurrence (BCR) is considered a decisive risk factor for clinical recurrence and the metastasis of prostate cancer (PCa). Therefore, we developed and validated a signature which could be used to accurately predict BCR risk and aid in the selection of PCa treatments. METHODS: A comprehensive genome-wide analysis of data concerning PCa from previous datasets of the Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) was performed. Lasso and Cox regression analyses were performed to develop and validate a novel signature to help predict BCR risk. Moreover, a nomogram was constructed by combining the signature and clinical variables. RESULTS: A total of 977 patients were involved in the study. This consisted of patients from the TCGA (n=405), GSE21034 (n=131), GSE70770 (n=193) and GSE116918 (n=248) datasets. A 9-mRNA signature was identified in the TCGA dataset (composed of C9orf152, EPHX2, ASPM, MMP11, CENPF, KIF4A, COL1A1, ASPN, and FANCI) which was significantly associated with BCR (HR =3.72, 95% CI: 2.30-6.00, P<0.0001). This signature was validated in the GSE21034 (HR =7.54, 95% CI: 3.15-18.06, P=0.019), GSE70770 (HR =2.52, 95% CI: 1.50-4.22, P=0.0025) and GSE116918 datasets (HR =4.75, 95% CI: 2.51-9.02, P=0.0035). Multivariate Cox regression and stratified analysis showed that the 9-mRNA signature was a clinical factor independent of prostate-specific antigen (PSA), Gleason score (GS), or AJCC T staging. The mean AUC for 5-year BCR-free survival predictions of the 9-mRNA signature (0.81) was higher than the AUC for PSA, GS, or AJCC T staging (0.52-0.73). Furthermore, we combined the 9-mRNA signature with PSA, GS, or AJCC T staging and demonstrated that this could enhance prognostic accuracy. CONCLUSIONS: The proposed 9-mRNA signature is a promising biomarker for predicting BCR-free survival in PCa. However, further controlled trials are needed to validate our results and explore a role in individualized management of PCa.