15-Gene Signature Predicts RFS, DFS in Patients With ccRCC

To help risk stratify clear cell renal cell carcinoma (ccRCC), Rohit Mehra, MD, and colleagues developed a gene expression signature to predict recurrence-free survival (RFS) and disease-free survival (DFS) in this patient population.

A discovery cohort was developed using 110 patients who had undergone radical nephrectomy for ccRCC. A 15-fold lasso and elastic-net regularized linear Cox model was used to develop the predictive gene expression signature.

Researchers derived a 31-gene cell cycle progression score using RNA sequencing data from each patient. Kaplan-Meier curves and multivariable Cox proportional hazard testing were used to validate the independent prognostic impact of the gene expression signature on DFS, disease-specific survival (DSS), and overall survival (OS) in 2 validation datasets (combined n=761).

The discovery cohort included 50 patients with recurrence and 41 patients without, with a median follow-up time of 26 and 36 months, respectively. The developed 15-gene signature was independently associated with worse DFS and DSS (DFS: hazard ratio [HR], 11.08 [95% CI, 4.9-25.1]; DSS: HR, 9.67 [95% CI, 3.4-7.7]) in a multivariable model.

The 15-gene signature was also independently associated with worse DFS and DSS in both validation data sets (validation A [n=382], DFS: HR, 2.6 [95% CI, 1.6-4.3]; DSS: HR, 3.0 [95% CI, 1.4-6.1] and validation B (n=379), DFS: HR, 2.1 [95% CI, 1.2-3.6]).

Pending further validation, this 15-gene signature has been initially validated to improve the risk stratification of patients with ccRCC and provide better treatment allocation.