A novel 8-gene panel for prediction of early biochemical recurrence in patients with prostate cancer after radical prostatectomy

Approximately 25% of prostate cancer (PCa) cases experience biochemical recurrence (BCR) following radical prostatectomy (RP). The patients with BCR, especially with BCR <= 2 year after RP (early BCR), are more likely to develop clinical metastasis and castration resistance. Now decision-making regarding BCR after RP relies solely on clinical parameters. We thus attempted to establish an early BCR-risk prediction model by combining a molecular signature with clinicopathological features for guiding clinical decision-making. In this study, an 8-gene signature was derived, and these eight genes were SPTBN2, LGI3, TGM3, LENG9, HAS3, SLC25A27, PCDHGA1, and ADPRHL1. The Kaplan-Meier analysis revealed a significantly prolonged BCR-free survival in the patients with low-risk scores compared to those with high-risk scores in both training and validation datasets. Harrell's concordance index and time-dependent receiver operating characteristic analysis demonstrated that this gene signature tended to outperform three commercial panels at early BCR prediction. Moreover, this signature was also proven as an independent predictor of BCR-free survival. A nomogram, incorporating the gene signature and clinicopathologic features, was constructed and excellently predicted 1-, 2- and 3-year BCR-free survival of localized PCa patients after RP. Gene set enrichment analysis, tumor immunity, and mRNA expression profiling analysis showed that the high-risk group was more prone to the immunosuppressive microenvironment and impaired DNA damage response than the low-risk group. Collectively, we successfully developed a novel 8-gene signature as a powerful predictor for early BCR after RP and created a prognostic nomogram, which may help inform the clinical management of PCa.

Automated summary

By combining a molecular signature with clinicopathological features, we successfully developed a predictive model for early biochemical recurrence (BCR) after radical prostatectomy (RP), which consists of an 8-gene signature. This gene signature outperformed three commercial panels in predicting early BCR and was proven to be an independent predictor of BCR-free survival. Furthermore, a prognostic nomogram incorporating the gene signature and clinicopathologic features was constructed, showing excellent predictive ability for BCR-free survival in localized prostate cancer patients after RP. The study also revealed that the high-risk group was more susceptible to immune suppression and impaired DNA damage response.