Gene Signature Sets Predict Recurrence, Chemotherapy Benefit in Stage 2 Colorectal Cancer

Hallmark-base gene signature sets (CSS sets) are more accurate and robust predictors of prognosis and identification of patients with stage 2 colorectal cancer (CRC) who would benefit from fluoropyrimidine-based adjuvant therapy, according to an article published online ahead of print in JAMA Oncology.¹

The topic of adjuvant therapy for patients with stage 2 CRC has been a controversial issue throughout the past 2 decades. Researchers sought to develop combinatory cancer hallmark-based CSS sets that could accurately predict prognosis and identify a subset of patients who would benefit from adjuvant chemotherapy.

Researchers analyzed 13 retrospective studies, which included 1,005 patients with stage 2 CRC who had clinical follow-up and adjuvant chemotherapy. Three independent cohorts had patients treated with fluorouracil-based adjuvant therapy.

Researchers identified 8 cancer hallmark-based gene signatures (30 genes each) to construct CSS sets for determination of prognosis.

The sets were validated in 11 cohorts of 767 patients who did not receive adjuvant chemotherapy. Results showed that CSS sets accurately grouped patients into low- (60% of patients), intermediate- (28%), and high-risk (12%) groups.

Five-year relapse survival rates were 94%, 78%, and 45%, respectively. The patients who received fluorouracil-based adjuvant chemotherapy had a survival benefit: recurrence rates were reduced by 30% to 40% in 5 years.

Reference

1. Gao S, Tibiche C, Zou J, et al. Identification and construction of combinatory cancer hallmark-based gene signature sets to predict recurrence and chemotherapy benefit in stage II colorectal cancer [published online ahead of print October 22, 2015]. JAMA Oncol. doi: 10.1001/jamaoncol.2015.3413.