Long-term validation of a molecular progression-associated gene classifier for prediction of muscle invasion in primary non-muscle-invasive bladder cancer

Abstract

Our previous study reported a clinically applicable prognostic gene classifier for primary non-muscle-invasive bladder cancer (NMIBC). The present study aimed to perform long-term validation of this classifier in the prediction of muscle-invasive disease. Previously published gene expression profiles were used from 176 patients with NMIBC with extended follow-up. Progression was defined as development of muscle invasion or metastasis, and the progression risk score was calculated using the previously developed eight-gene progression classifier. During median follow-up of 72.8 (interquartile range, 37.0-118.7) months, 26 (14.8%) patients progressed to muscle-invasive bladder cancer. The molecular progression risk score was significantly associated with clinicopathological variables, including tumor number, stage, grade and multivariate risk assessment tools (P<0.05 in each case). Multivariate Cox regression analysis revealed that molecular progression risk score was an independent predictor of development of invasive tumor, either as a continuous variable [hazard ratio (HR), 1.489; 95% confidence interval (CI), 1.216-1.823; P<0.001] or as a categorical variable (HR, 5.026; 95% CI, 1.619-15.608; P=0.005). In conclusion, the present results confirmed the clinical utility of the progression-associated gene classifier for prediction of development of muscle invasion in NMIBC. The molecular progression risk score may aid in selecting patients who could benefit from more aggressive therapeutic intervention.

Keywords: bladder cancer; gene signature; progression; risk score.

Figure 1.

Kaplan-Meier estimation of development of muscle-invasive tumors in primary non-muscle-invasive bladder cancer, according to a molecular progression risk score based on quantitative polymerase chain reaction.