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.

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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.

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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.


  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.