title: miR-200c overexpression is associated with better efficacy of EGFR-TKIs in non-small cell lung cancer patients with EGFR wild-type.
abstract: Several randomized trials have demonstrated non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations can achieve favorable clinical outcomes on treatment with EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation is considered as a predictive marker for efficacy of EGFR-TKIs in NSCLC. Here we show miR-200c overexpression was correlated with the epithelial phenotype and sensitivity to gefitinib in EGFR wild-type NSCLC cell lines. Up-regulated miR-200c could regain the sensitivity to gefitinib in the EGFR wild-type cell lines and miR-200c could regulate epithelial to mesenchymal transition through PI3K/AKT and MEK/ERK pathways. NSCLC patients at advanced stage (N=150) who received EGFR-TKIs (gefitinib or erlotinib) as second- or third-line therapy from September 2008 to December 2012 were included in the study. In 66 NSCLC patients with wild-type EGFR, high levels of miR-200c expression was associated with higher disease control rate (DCR), longer progression-free survival (PFS) and longer overall survival (OS) compared with low miR-200c expression subgroup. In the subgroup with EGFR mutation, the trend remained the same but not statistically significant. Overall, these findings indicated that miR-200c might be a predictive biomarker for sensitivity to EGFR-TKIs in advanced NSCLC patients with wild-type EGFR.
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Yishi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Mingchuan
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Respiration, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Cheng
authors.affiliation: Department of Central Laboratory, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
authors.forename: Yinmin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Departments of Medicine and Pathology, University of Colorado Cancer Center, Aurora, Colorado, USA.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors