title: microRNA expression profiles associated with survival, disease progression, and response to gefitinib in completely resected non-small-cell lung cancer with EGFR mutation.
abstract: microRNAs have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that some microRNAs can function as oncogenes or tumor suppressors, the role of microRNAs in mediating cancer progression remains unexplored. And whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic or predictive biomarkers in radically resected non-small-cell lung carcinoma (NSCLC) patients still needs to be further validated. Our analyses involved two separated, retrospective cohorts. Firstly, microRNA expression profile was performed in a cohort consisted of 128 radically resected NSCLC patients [60 were positive to epidermal growth factor receptor (EGFR) mutation and 68 were negative] and 32 healthy providers to identify EGFR mutation-related microRNAs and to determine their association with survival. In addition, to validate our findings, we used quantitative reverse transcriptase polymerase chain reaction assays to measure microRNAs and assess their association with disease progression, survival, and response to gefitinib in an independent cohort of 201 patients with EGRF mutation. In radically resected NSCLC patients, the expression levels of miR-21, 10b in patients with EGFR mutation were much higher than those without mutation. We used Cox proportional-hazards regression to evaluate the effect of treatment on survival. In both univariate and multivariate analyses, gefitinib was associated with a significant improvement in overall survival in patients with reduced miR-21 expression. Thus, miR-21 expression emerged as an independent predictor of the response to gefitinib. Additionally, miR-10b is highly expressed in progressive disease compared with complete remission or stable disease (P < 0.001). However, miR-21 expression has no significant prognosis for disease progression (P = 0.720). Meanwhile, when overall survival was considered as the end point, miR-10b did not have a significant difference between different subgroups (P = 0.634). The expression patterns of microRNAs differ significantly between patients with positive and negative EGFR mutation. And the expression status of miR-21 and 10b in such patients is associated with disease progression, survival, and response to adjuvant therapy with gefitinib.
authors.affiliation: Medical College, Thoracic Surgery of the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.forename: Dongfang
authors.initials: D
authors.lastname: Tang
authors.forename: Ruyong
authors.initials: R
authors.lastname: Yao
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Wang
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Wang
authors.forename: Yasai
authors.initials: Y
authors.lastname: Yao
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Li
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib