title: The expression of microRNA-34a is inversely correlated with c-MET and CDK6 and has a prognostic significance in lung adenocarcinoma patients.
abstract: We aimed to establish whether the expression of microRNA-34a (miR-34a) is correlated with that of c-MET and G1 phase regulators such as cyclin dependent kinase (CDK) 4, CDK6, and cyclin D (CCND) 1 in non-small cell lung cancer (NSCLC), and whether a relationship exists between miR-34a expression and both clinicopathologic factors and recurrence-free survival (RFS). For 58 samples archived from NSCLC patients, we measured the expression of miR-34a and c-MET, CDK4/6, and CCND1 by quantitative RT-PCR and assessed the relationship between miR-34a expression, clinicopathological factors, and RFS. The expression of miR-34a was significantly lower in squamous cell tumors (P < 0.001) and in tumors associated with lymphatic invasion (P = 0.001). We found significant inverse correlations between miR-34a and c-MET (R = -0.316, P = 0.028) and CDK6 expression (R = -0.4582, P = 0.004). RFS were longer in adenocarcinoma patients with high miR-34a expression than in those with low miR-34a expression (55.6 vs. 21.6 months; P = 0.020). With univariate analysis, statistically significant prognostic factors for RFS in adenocarcinoma patients were miR-34a expression (Relative risk (RR), 8.14; P = 0.049), TNM stage (RR, 13.55; P = 0.001), LN metastasis (RR, 4.19; P = 0.043), and the presence of lymphatic invasion (RR, 7.05; P = 0.015). In multivariate analysis, only miR-34a was prognostic for RFS (RR, 11.5; P = 0.027). miR-34a expression was inversely correlated with that of c-MET and CDK6 in NSCLC, and had prognostic significance for RFS, especially in adenocarcinoma patients.
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Banpo-Daero 222, Seocho-Gu, Seoul, 137-701, Republic of Korea.
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Kang San
authors.initials: KS
authors.lastname: Roh
authors.affiliation: South Sea Environment Research Department, Korea Institute of Ocean Science and Technology, Geoje, Republic of Korea.
authors.forename: Sung-Suk
authors.initials: SS
authors.lastname: Suh
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Sukchan
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Thoracic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sook Whan
authors.initials: SW
authors.lastname: Sung
authors.affiliation: Department of Thoracic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jae Kil
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Banpo-Daero 222, Seocho-Gu, Seoul, 137-701, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Byun
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Banpo-Daero 222, Seocho-Gu, Seoul, 137-701, Republic of Korea. jinkang@catholic.ac.kr.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6
keywords: Adenocarcinoma of the lung; Cyclin-dependent kinase 6; c-MET; miR-34a