Measurement of Gene Expression Could Tailor Colorectal Cancer Treatment

Measuring the expression of two genes, ERCC1 and TS, could help physicians in assigning metastatic colorectal cancer patients to chemotherapy that would be of the most benefit, according to the results of a small retrospective study published in PLOS One.

Researchers led by Michel B. Choueiri, MD, of the University of California, San Diego, showed that patients with high ERCC1/TS expression had a poor prognosis compared with those with low expression and that low ERCC1/TS expression was predictive of response to treatment with FOLFOX chemotherapy, but not FOLFIRI chemotherapy.

In the study, the researchers used the commercially available test ResponseDX: Colon to conduct gene expression analysis for ERCC1 and TS in 41 patients with metastatic colon cancer diagnosed between July 2008 and August 2013. They also used data from the Cancer Genome Atlas to link gene expression information with survival data.

Choueiri and colleagues found that patients with low expression of ERCC1 had a median overall survival of 36 months compared with 10.1 months in those with high expression (hazard ratio [HR] = 0.29; 95% confidence interval [CI], 0.095–0.84). Those with low expression also had a longer median time to treatment failure after first-line chemotherapy (14.1 vs 2.4 months; HR = 0.17; 95% CI, 0.048–0.58). A significant association between low ERCC1 expression and survival remained even after the researchers adjusted for other factors, including age, sex, tumor grade, and Eastern Cooperative Oncology Group (ECOG) performance status.

Similar associations between TS expression and survival were also found. Patients with low TS expression had significantly longer overall survival compared with patients with high levels of TS expression (36.0 vs 14.8 months; HR = 0.25; 95% CI, 0.074–0.82).

“Patients with an elevated level of both ERCC1 and TS had a trend towards lower overall response rate of 50% compared to 63% in patients with low ERCC1/high TS and 86% in patients with low levels of both markers,” the researchers wrote.

Choueiri and colleagues then looked at levels of ERCC1 and TS expression as they related to patient response to first-line chemotherapy. They found that low expression of both genes predicted response in patients treated with FOLFOX (40% vs 91%), but not with FOLFIRI (71% vs 71%).

“This study demonstrates the potential utility of ERCC1 and TS gene expression as prognostic and possibly predictive biomarkers in metastatic colorectal cancer, consistent with prior studies,” the researchers wrote. “In the future the prognostic and predictive value of ERCC1 and TS expression should be examined in the context of a larger prospective clinical trial.”