FCGR2A, FCGR3A polymorphisms and therapeutic efficacy of anti-EGFR monoclonal antibody in metastatic colorectal cancer
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Hou-Qun Ying1,2,*, Feng Wang2,*, Xiao-Lin Chen4,*, Bang-Shun He2, Yu-Qin Pan2, Chen Jie2,3, Xian Liu2, Wei-Jun Cao5, Hong-Xin Peng1, Kang Lin2, Shu-Kui Wang2
1Medical College, Southeast University, Nanjing 210009, Jiangsu, China
2Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
3Life Scientific College, Nanjing Normal University, Nanjing 210046, Jiangsu, China
4Department of Clinical Laboratory, Pingxiang People's Hospital, Pingxiang, 337055, Jiangxi, China
5Department of Digestion, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu China
*These authors have contributed equally to this work
Shu-Kui Wang, e-mail: [email protected]
Keywords: H131R, F158V, FCGR, mCRC, anti-EGFR mAb
Received: April 30, 2015 Accepted: July 30, 2015 Published: August 11, 2015
Anti-EGFR monoclonal antibodies (mAb) such as cetuximab, panitumumab are one kind of efficacious targeted drugs in treatment of metastatic colorectal cancer (mCRC). However, only a small proportion of patients harbored wild-KRAS genotype can benefit from it. We hypothesized that personal genetic heterogeneity might be the main cause leading to obvious difference in its clinical efficacy. A retrospective study including 82 mCRC patients treated with chemotherapy plus cetuximab and a comprehensive meta-analysis containing 2831 cases within sixteen eligible studies were conducted to investigate the possible association between FCGR2A H131R and FCGR3A V158F and clinical outcome of mCRC patients treated with anti-EGFR mAb based therapy. Results of the retrospective study showed that H131R within FCGR2A or V158F within FCGR3A were not associated with clinical outcome in 82 KRAS wild chemorefractory mCRC patients in co-dominant, dominant, recessive, over-dominant, allele genetic models. However, the comprehensive meta-analysis with the largest of sample size obtained the significant result between FCGR3A V158F and PFS (FV/VV vs. FF: Ph = 0.027, MSR = 0.680, 95%CI = 0.549−0.842 in overall population; Ph = 0.12, MSR = 0.728, 95%CI = 0.648–0.818 in KRAS wild population) and OS (VV vs. FF: Ph < 0.001, MSR = 0.733, 95%CI = 0.578−0.930 in overall population). These findings indicate that KRAS wild chemorefractory mCRC individual harbored genotype FF of V158Fcan benefit from anti-EGFR mAb adjuvant therapy in terms of PFS and OS, and it may be useful genetic biomarker to predict clinical survival of mCRC individuals with anti-EGFR mAb based therapy.
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