Unique circulating microRNAs in relation to EGFR mutation status in Japanese smoker male with lung adenocarcinoma
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Sachio Ito1, Yoshihiro Kamoto1, Akiko Sakai1, Kaori Sasai1, Tatsuro Hayashi2,*, Shinichi Toyooka3,4 and Hiroshi Katayama1
1Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
2Division of Thoracic Surgery, National Hospital Organization, Yamaguchi-Ube Medical Center, Yamaguchi, Japan
3Department of Thoracic, Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
4Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
*Present address: Division of Respiratory Surgery, National Hospital Organization, Fukuyama Medical Center, Hiroshima, Japan
Sachio Ito, email: [email protected]
Hiroshi Katayama, email: [email protected]
Keywords: circulating miRNA, lung adenocarcinoma, EGFR gene mutation, smoking, male
Received: August 06, 2017 Accepted: September 11, 2017 Published: September 30, 2017
The incidence of lung adenocarcinoma has been increasing recently in smokers. The molecular target therapy has been developed for lung adenocarcinoma patients harboring EGFR gene mutation. However, the treatment modalities for patients without mutation are currently limited. Thus, analysis of EGFR gene mutation status at early stage is important strategy to classify the patients for improving treatments and prognosis efficiently. This study aimed to identify microRNA (miRNA) signature in relation to mutation status in EGFR gene in early stage of lung adenocarcinoma male patients with smoking history. MiRNA profiles were assessed by microarray in paired plasma and tissue pooled from 10 EGFR wild type (EGFR-wt) and 10 EGFR mutated (EGFR-mut) patients. Expressions of selected miRNAs were verified further by real-time qRT-PCR in 83 plasma samples consisting of 55 EGFR-wt patients and 28 EGFR-mut patients and their correlation with clinicopathological parameters and EGFR gene mutation status were evaluated. We found that seven miRNAs (miR-16-5p, miR-23a-3p, miR-103a-3p, miR122-5p, miR-223-3p, miR-346 and miR-451a) were differentially expressed in stage I and stage I+II. Especially, miR-23a-3p was only miRNA shown higher expression in EGFR-wt patients than EGFR-mut patients. Thus, our findings could be useful non-invasive biomarkers to differentiate mutation status in EGFR gene in smoker lung adenocarcinoma male patients.
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