title: Circulating miRNAs is a potential marker for gefitinib sensitivity and correlation with EGFR mutational status in human lung cancers.
abstract: miRNA expression is deregulated in non-small cell lung cancer (NSCLC), and some miRNAs are associated with gefitinib sensitivity. Here, we investigated if circulating miRNAs could be a useful biomarker for the prediction of EGFR mutation and the patient's prognosis. The differential miRNAs related to gefitinib sensitivity were screened and identified by microRNA array. Using Taqman-based real-time RT-PCR, we analyzed the expression of selected miRNAs in tumor tissues and plasma of 150 NSCLC patients. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to determine the association between miRNAs expression and survival. Receiver operating characteristic curve analysis was also performed. Compared with PC9 cell line, 41 microRNAs detected by microarray were significantly differentially expressed in A549 and H1299 cells. The 5 selected hsa-miRNAs were all found differently expressed between wild and mutant EGFR carriers (all P<0.01). Down-regulation of 5 selected miRNAs were independently associated with lymphatic invasion (all P<0.01) and clinical stage (all P<0.01), respectively. Both down-regulation of has-miR-195 (P=0.012) and has-miR-21 (P=0.004) were associated with poor differentiation. All up-regulation of 5 has-miRNAs were associated with smoking (All P<0.05). 5 hsa-miRNAs were up-regulated both in plasma and tissue samples. A model including 4 hsa-miRNAs may predict EGFR mutational status and gefitinib-sensitivity (both AUC: 0.869). Plasma levels of has-miR-125b expression were associated with disease-free survival (P=0.033) and overall survival in the patients (P=0.028). In a word, Circulating 5 selected miRNAs may especially be useful in predicting EGFR mutation, and circulating hsa-miR-125b may have prognostic values in NSCLC patients.
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China ; Department of Thoracic Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China ; Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus) Hangzhou 310022, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China ; The Affiliated Tumor Hospital of Zhejiang Chinese Medical University Zhejiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China.
authors.forename: Xian-Cong
authors.initials: XC
authors.lastname: Huang
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China.
authors.forename: Lie-Hao
authors.initials: LH
authors.lastname: Jiang
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China.
authors.forename: Xiu-Xiu
authors.initials: XX
authors.lastname: Hou
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China ; Department of Thoracic Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China ; Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus) Hangzhou 310022, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Mao
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China ; Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus) Hangzhou 310022, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ling
keywords: EGFR mutation; Non-small cell lung cancer (NSCLC); acquired resistance; gefitinib; miRNAs