miR-200c overexpression is associated with better efficacy of EGFR-TKIs in non-small cell lung cancer patients with EGFR wild-type
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Jiayu Li1, Xuefei Li2, Shengxiang Ren1, Xiaoxia Chen1, Yishi Zhang1, Fei Zhou1, Mingchuan Zhao1, Chao Zhao2, Xiu Chen3, Ningning Cheng1, Yinmin Zhao4, Caicun Zhou1, Fred R. Hirsch5
1 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, China
2 Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, China
3 Department of Respiration, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China
4 Department of Central Laboratory, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China
5 Departments of Medicine and Pathology, University of Colorado Cancer Center, Aurora, Colorado, USA.
Dr. Caicun Zhou, e-mail: [email protected]
Key Words: Non-small cell lung cancer, MiR-200c, Epidermal growth factor receptor, Wild type, Tyrosine-kinase inhibitor
Received: July 05, 2014 Accepted: July 29, 2014 Published: August 08, 2014
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.
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