title: FCGR2A, FCGR3A polymorphisms and therapeutic efficacy of anti-EGFR monoclonal antibody in metastatic colorectal cancer.
abstract: 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.
authors.affiliation: Medical College, Southeast University, Nanjing 210009, Jiangsu, China.|Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
authors.forename: Hou-Qun
authors.initials: HQ
authors.lastname: Ying
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Pingxiang People's Hospital, Pingxiang, 337055, Jiangxi, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
authors.forename: Bang-Shun
authors.initials: BS
authors.lastname: He
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
authors.forename: Yu-Qin
authors.initials: YQ
authors.lastname: Pan
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.|Life Scientific College, Nanjing Normal University, Nanjing 210046, Jiangsu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Jie
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Digestion, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Cao
authors.affiliation: Medical College, Southeast University, Nanjing 210009, Jiangsu, China.
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Peng
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Lin
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
authors.forename: Shu-Kui
authors.initials: SK
authors.lastname: Wang
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D017452:Receptors, IgG / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: F158V; FCGR; H131R; anti-EGFR mAb; mCRC