Evaluation of a 24‐gene signature for prognosis of metastatic events and prostate cancer‐specific mortality

Abstract

OBJECTIVES To determine the prognostic potential of Sig24 for identifying prostate cancer patients at risk of developing metastases or experiencing PCSM following radical prostatectomy. SUBJECTS AND METHODS Sig24 scores were calculated from previously collected gene expression microarray data from the Cleveland Clinic and Mayo Clinic (I and II). The performance of Sig24 was determined using time-dependent c-index analysis, Cox proportional hazards regression and Kaplan-Meier survival analysis. RESULTS Higher Sig24 scores were significantly associated with higher pathologic Gleason scores (GS) in all three cohorts. Analysis of the Mayo Clinic II cohort, which included time to event information, indicated that patients with high Sig24 scores also had an increased risk of developing metastasis (HR: 3.78, 95% CI: 1.96–7.29, p < 0.001) or experiencing PCSM (HR: 6.54, 95% CI: 2.16–19.83, p < 0.001). CONCLUSIONS The findings of this study demonstrate the applicability of Sig24 for the prognosis of metastasis or PCSM following radical prostatectomy. Future studies investigating the combination of Sig24 with available prognostic tests may provide new approaches to improve risk stratification for patients with prostate cancer.

A Novel Gene Signature-Based Model Predicts Biochemical Recurrence-Free Survival in Prostate Cancer Patients after Radical Prostatectomy

“…Nowadays, advancements in high-throughput techniques such as microarray and RNA-sequencing (RNA-seq) have provided new insights into transcriptome profiling, which facilitate the utilization of molecules as diagnostic and prognostic biomarkers [8,9]. Some studies have established gene signatures to help distinguish aggressive PCa tumors or improve survival prediction in PCa patients [10][11][12]. However, most of these signatures exhibit a prognostic value without having a direct impact on treatment decision-making.…”

Predicting outcome: role of gene signatures

“…This 24‐gene signature forms the basis of the present study by Pellegrini et al. , who refer to this gene signature as Sig24. In their study, they firstly undertook to determine if Sig24 was associated with pathological Gleason score as a marker of tumour aggressiveness, and then if it had prognostic value for the identification of patients at risk of metastasis or prostate cancer‐specific mortality after radical prostatectomy.…”

Development and internal validation of a novel model and markers to identify the candidates for lymph node metastasis in patients with prostate cancer

“…Jin et al [22] demonstrated that an NF-kB-activated recurrence predictor 21 gene signature could predict disease-specific survival and distant metastasis-free survival in patients with PCa, although the study used molecular biological methods. Recently, another study [23] identified a 24-gene signature that was significantly associated with the development of metastasis and prostate cancer-specific mortality after radical prostatectomy. However, the importance of gene signatures in predicting LNI in PCa is not fully understood.…”