Developing a Biopsy-Based 6-Gene Signature to Risk-Stratify Patients With Early-Stage Prostate Cancer

Many patients with prostate cancer (PCa) are commonly treated with surgery (radical prostatectomy, RP) or radiation therapy, options that are associated with a significant reduction in quality of life. While molecular signatures can assist in stratification to determine the risk of aggressive PCa, prognostic capacity can be improved.

Researchers identified a panel of 14 prognostic genes from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) database in order to develop and validate a novel, biopsy-based 6-gene signature to accurately risk-stratify patients with early-stage PCa and facilitate treatment decision-making. They presented their work at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Gene expression was measured by analyzing reverse-transcription quantitative polymerase chain reaction in RP samples taken from an Irish cohort of patients diagnosed with PCa and treated with RP (n=426). A cross-validated logistic regression analysis identified a 6-gene molecular risk score (MRS) with strong prognostic performance to predict aggressive PCa, such as adverse pathology (AP), at RP or biochemical recurrence (BCR).

The MRS was combined with Cancer of the Prostate Risk Assessment (CAPRA) scores to create a molecular plus clinical risk score (MCRS). The MRS and MCRS were validated in biopsy samples from an independent Swedish cohort of men diagnosed with PCa and treated by RP (n=100).

A 6-gene signature comprising 4 prognostic genes and 2 reference genes was identified to improve prognostic value over clinical features. In the clinical biopsy validation study univariable analysis, the area under the curve of the signature for AP was 0.72 (MRS) and 0.82 (MCRS) versus 0.72 for European Association of Urology (EAU) risk categories and 0.82 for CAPRA.

The C-index for BCR was 0.62 (MRS) and 0.74 (MCRS) versus 0.65 for EAU risk categories and 0.73 for CAPRA. In bivariable analysis, the 6-gene signature added statistically significant (P<.001) prognostic value to EAU risk categories and CAPRA.

The 6-gene prognostic signature showed a strong performance for AP and BCR in an independent clinical biopsy validation study, demonstrating that MCRS can improve prognostic stratification and inform optimal patient management after diagnosis.