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Open Access 01-12-2018 | Research article

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

Authors: Zhu Mei, Yang W. Shao, Peinan Lin, Xiaomin Cai, Biao Wang, Yan Ding, Xiangyuan Ma, Xue Wu, Yewei Xia, Dongqin Zhu, Yongqian Shu, Zan Fu, Yanhong Gu

Published in: BMC Cancer | Issue 1/2018

Abstract

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.

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Title: SMAD4 and NF1 mutations as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese metastatic colorectal cancer patients
Authors: Zhu Mei
Yang W. Shao
Peinan Lin
Xiaomin Cai
Biao Wang
Yan Ding
Xiangyuan Ma
Xue Wu
Yewei Xia
Dongqin Zhu
Yongqian Shu
Zan Fu
Yanhong Gu
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-018-4298-5

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