title: DNA methylation mediated silencing of microRNA-145 is a potential prognostic marker in patients with lung adenocarcinoma.
abstract: The molecular mechanism of down-regulated microRNA-145 (miR-145) expression in lung adenocarcinoma (LAC) remains largely unknown. We hypothesized that aberrant hyper-methylation of the CpG sites silenced the expression of miR-145 in LAC. In consideration of its pivotal role in LAC development and progression, we also evaluated the clinical utility of miR-145 as a prognostic marker. We assessed the DNA methylation status of the miR-145 promoter region in 20 pairs of LAC and the matched non-tumor specimens. We subsequently applied our own LAC tissue microarray containing 92 pairs of tumor and non-tumor tissues with long time follow-up records to evaluate whether miR-145 is a potential prognostic marker in LAC. The Sequenom EpiTYPER MassArray analysis showed that miR-145 was down-regulated in human LAC tissues accompanied by increased DNA methylation of its upstream region, which was further validated by the data from TCGA database. Significance was observed between miR-145 expression and clinic-pathologic parameters. Univariate and multivariate analysis revealed that miR-145 expression level was an independent risk factor for both OS and DFS in LAC patients. Taken together, DNA hyper-methylation in the miR-145 promoter region reduced its expression in LAC and miR-145 expression level might serve as a novel prognostic biomarker.
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, P.R. China, 210009.|The Fourth Clinical College of Nanjing Medical University, Nanjing 210000, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xia
authors.affiliation: The Fourth Clinical College of Nanjing Medical University, Nanjing 210000, China.|Department of Thoracic Surgery, Xuzhou Centre Hospital.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, P.R. China, 210009.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, P.R. China, 210009.|The Fourth Clinical College of Nanjing Medical University, Nanjing 210000, China.
authors.forename: Qixing
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, P.R. China, 210009.
authors.forename: Gaochao
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, P.R. China, 210009.|The Fourth Clinical College of Nanjing Medical University, Nanjing 210000, China.
authors.forename: Run
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, P.R. China, 210009.
authors.forename: YanYan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, P.R. China, 210009.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, P.R. China, 210009.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D030541:Databases, Genetic; D018572:Disease-Free Survival; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; C541010:MIRN145 microRNA, human; D035683:MicroRNAs