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

Content Provider	Springer Nature : BioMed Central
Author	Mei, Zhu Shao, Yang W. Lin, Peinan Cai, Xiaomin Wang, Biao Ding, Yan Ma, Xiangyuan Wu, Xue Xia, Yewei Zhu, Dongqin Shu, Yongqian Fu, Zan Gu, Yanhong
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 (SMAD4mut, n = 8) or NF1 mutations (NF1mut, n = 4) had significantly shorter PFS comparing to those carrying wildtype SMAD4 (SMAD4wt, n = 25) (P = 0.0081) or wildtype NF1 (NF1wt, n = 29) (P = 0.0028), respectively. None of the SMAD4mut or NF1mut patients showed response to cetuximab when assessed at 12-week post-treatment. Interestingly, two patients carrying both SMAD4mut and NF1mut 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.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-018-4298-5.pdf
Ending Page	7
Page Count	7
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-018-4298-5
Journal	BMC Cancer
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2018-04-27
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health SMAD4 NF1 Metastatic colorectal cancer Cetuximab Prognosis Next-generation sequencing Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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