Sho S, et al. – In the study presented here, a prognostic tumor mutational profile that could predict colorectal cancer (CRC) recurrence was identified. The proposed mutation panel identified CRC patients at high–risk for recurrence, which could help guide adjuvant therapy and post–operative surveillance protocols.

Methods

• For this purpose, whole-exome sequencing data were acquired for two hundred seven patients with stage II/III CRC from The Cancer Genome Atlas.
• Mutational landscape in relapse-free versus relapsed cohort was compared utilizing Fisher's exact test, followed by multivariate Cox regression to identify genes related to cancer recurrence.
• Bootstrap-validation was utilized to investigate internal/external validity.

Results

• Five prognostic genes (APAF1, DIAPH2, NTNG1, USP7, and VAV2) were identified, which were combined to form a prognostic mutation panel.
• It was observed in the findings that patients with ≥1 mutation(s) within this five-gene panel had worse prognosis (3-yr relapse-free survival [RFS]: 53.0%), compared to patients with no mutation (3-yr RFS: 84.3%).
• In multivariate analysis, the five-gene panel remained prognostic for cancer recurrence independent of stage and high-risk features (hazard ratio 3.63, 95%CI [1.93-6.83], P < 0.0001).
• Moreover, its prognostic accuracy was better than the American Joint Commission on Cancer classification (concordance-index: 0.70 vs 0.54).