title: Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma.
abstract: DNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined. This concurrent analysis identified 21 negatively correlated probes (r ≤ -0.5), corresponding to 17 genes. Examining the endogenous expression in lung cancer cell lines, five of the genes were found to be significantly down-regulated. Furthermore, in tumor cells alone, 5-aza-2'-deoxycytidine treatment increased the expression levels of STXBP6 in a dose dependent manner and pyrosequencing showed higher percentage of methylation in STXBP6 promoter. Functional analysis revealed that overexpressed STXBP6 in A549 and H1299 cells significantly decreased cell proliferation, colony formation, and migration, and increased apoptosis. Finally, significantly lower survival rates (P < 0.05) were observed when expression levels of STXBP6 were low. Our results provide a basis for the genetic etiology of lung adenocarcinoma by demonstrating the possible role of hypermethylation of STXBP6 in poor clinical outcomes in lung cancer patients.
authors.affiliation: Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Govinda
authors.initials: G
authors.lastname: Lenka
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.|Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Mong-Hsun
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Jen-Hao
authors.initials: JH
authors.lastname: Hsiao
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Tzu-Pin
authors.initials: TP
authors.lastname: Lu
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jang-Ming
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Division of Thoracic Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.|Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Liang-Chuan
authors.initials: LC
authors.lastname: Lai
authors.affiliation: Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.|School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Chuang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D059467:Transcriptome; D014410:Tumor Stem Cell Assay
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C465215:STXBP6 protein, human