MicroRNA expression profiles and clinicopathological implications in lung adenocarcinoma according to EGFR , KRAS, and ALK status

// Hyojin Kim 1 , Jeong Mi Yang 1 , Yan Jin 1 , Sanghoon Jheon 2 , Kwhanmien Kim 2 , Choon Taek Lee 3 , Jin-Haeng Chung 1 , Jin Ho Paik 1 1 Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea 2 Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea 3 Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Correspondence to: Jin Ho Paik, email: paikjh@snu.ac.kr Jin-Haeng Chung, email: chungjh@snu.ac.kr Keywords: microRNA, lung cancer, adenocarcinoma, miR-342-3p, ALK Received: May 30, 2016     Accepted: December 01, 2016     Published: December 27, 2016 ABSTRACT Lung adenocarcinoma has distinctive clinicopathological features that are related to specific genetic alterations, including EGFR and KRAS mutations and ALK rearrangement. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate many important biological processes and influence cancer phenotypes. This study retrospectively investigated microRNA expression profiles, and their clinicopathological implications, in lung adenocarcinoma according to genetic status ( EGFR , KRAS , ALK , and triple negative). A total of 72 surgically resected lung adenocarcinoma specimens (19 EGFR- mutated, 17 KRAS -mutated, 16 ALK -rearranged, and 20 triple negative cancers) were screened for 23 microRNAs using quantitative real-time reverse transcriptase polymerase chain reaction. We then evaluated the associations between the microRNA expressions and the cancers’ genetic and clinicopathological features. Eight microRNAs were associated with clinicopathological features, such as male sex and ever-smoker status (high miR-373-3p, miR-1343-3p, miR-138-1-3p, and miR-764; low miR-27b-3p) and vascular invasion (high miR-27b-3p; low miR-1343-3p and miR-764). Clustering and discriminant analyses revealed that the microRNA expression patterns in the ALK group were different from those in the EGFR and KRAS groups. Five microRNAs (high miR-1343-3p; low miR-671-3p, miR-103a-3p, let-7e, and miR-342-3p) were especially distinctive in the ALK group, compared to the EGFR and KRAS groups. Moreover, a significant association was observed between ALK -rearrangement, decreased miR-342-3p expression, and immunohistochemical loss of E-cadherin. Therefore, microRNA expression profiles appear to have distinctive clinicopathological implications in ALK- rearranged lung adenocarcinoma. Furthermore, the association of ALK rearrangement, decreased miR-342-3p expression, and E-cadherin loss might indicate that miR-342-3p is involved in the ALK -associated phenotypes and epithelial-mesenchymal transition.