SMAD4 and NF1 mutations as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese metastatic colorectal cancer patients

BACKGROUND: Cetuximab, an anti-EGFR monoclonal antibody, is used in combination with chemotherapy in clinic to enhance the outcome in metastatic colorectal cancer (mCRC) patients with only ~ 20% response rate. To date only activating mutations in KRAS and NRAS have been identified as poor prognosis biomarkers in cetuximab-based treatment, which makes an urgent need for identification of novel prognosis biomarkers to precisely predict patients’ response in order to maximize the benefit. METHODS: In this study, we analysed the mutation profiles of 33 Chinese mCRC patients using comprehensive next-generation sequencing (NGS) targeting 416 cancer-relevant genes before cetuximab treatment. Upon receiving cetuximab-based therapy, patients were evaluated for drug response, and the progression-free survival (PFS) was monitored. The association of specific genetic alterations and cetuximab efficacy was analyzed. RESULTS: Patients carrying SMAD4 mutations (SMAD4(mut), n = 8) or NF1 mutations (NF1(mut), n = 4) had significantly shorter PFS comparing to those carrying wildtype SMAD4 (SMAD4(wt), n = 25) (P = 0.0081) or wildtype NF1 (NF1(wt), n = 29) (P = 0.0028), respectively. None of the SMAD4(mut) or NF1(mut) patients showed response to cetuximab when assessed at 12-week post-treatment. Interestingly, two patients carrying both SMAD4(mut) and NF1(mut) showed the shortest PFS among all the patients. CONCLUSIONS: Our results demonstrated that SMAD4 and NF1 mutations can serve as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese mCRC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4298-5) contains supplementary material, which is available to authorized users.