Novel gene signature for predicting biochemical recurrence-free survival of prostate cancer and PRAME modulates prostate cancer progression.

ABSTRACT

Biochemical recurrence (BCR) is considered as an early sign of prostate cancer (PCa) progression after initial treatment, such as radical prostatectomy and radiotherapy; hence, it is important to stratify patients at risk of BCR. In this study, we established a robust 8-gene signature (APOF, Clorf64, RPE65, SEMG1, ARHGDIG, COMP, MKI67 and PRAME) based on the PCa transcriptome profiles in the Cancer Genome Atlas (TCGA) for predicting BCR-free survival of PCa, which was further validated in the MSK-IMPACT Clinical Sequencing Cohort (MSKCC) PCa cohort. Moreover, we found that one risk-related gene (PRAME) was upregulated in tumor samples, particularly in high-risk group was well as in patients metastatic tumor and was correlated with chemotherapeutic drug response. In vitro experiments showed that knocking down PRAME reduced the proliferation, migration, and invasion of PCa cells. Therefore, our study established a new 8-gene signature that could accurately predict the BCR risk of PCa. Inhibition of PRAME attenuated the proliferation, invasion, and migration of PCa cells. These findings provide a novel tool for stratifying high-risk PCa patient and shed light on the mechanism of PCa progression.