title: A prognostic predictor panel with DNA methylation biomarkers for early-stage lung adenocarcinoma in Asian and Caucasian populations.
abstract: BACKGROUND
  The incidence of lung adenocarcinoma (LUAD) is increasing worldwide with different prognosis even in early-stage patients. We aimed to identify a prognostic panel with multiple DNA methylation biomarkers to predict survival in early-stage LUAD patients of different racial groups.
  
  
  METHODS
  The methylation array, pyrosequencing methylation assay, Cox regression and Kaplan-Meier analyses were conducted to build the risk score equations of selected probes in a training cohort of 69 Asian LUAD patients. The risk score model was verified in another cohort of 299 Caucasian LUAD patients in The Cancer Genome Atlas (TCGA) database.
  
  
  RESULTS
  We performed a Cox regression analysis, in which the regression coefficients were obtained for eight probes corresponding to eight genes (AGTRL1, ALDH1A3, BDKRB1, CTSE, EFNA2, NFAM1, SEMA4A and TMEM129). The risk score was derived from sum of each methylated probes multiplied by its corresponding coefficient. Patients with the risk score greater than the median value showed poorer overall survival compared with other patients (p = 0.007). Such a risk score significantly predicted patients showing poor survival in TCGA cohort (p = 0.036). A multivariate analysis was further performed to demonstrate that the eight-probe panel association with poor outcome in early-stage LUAD patients remained significant even after adjusting for different clinical variables including staging parameters (hazard ratio, 2.03; p = 0.039).
  
  
  CONCLUSIONS
  We established a proof-of-concept prognostic panel consisting of eight-probe signature to predict survival of early-stage LUAD patients of Asian and Caucasian populations.
authors.affiliation: Department of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Pharmacology and Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, Taiwan.
authors.forename: I-Ying
authors.initials: IY
authors.lastname: Kuo
authors.affiliation: Department of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Pharmacology and Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, Taiwan.
authors.forename: Jayu
authors.initials: J
authors.lastname: Jen
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Pulmonary Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Lien-Huei
authors.initials: LH
authors.lastname: Hsu
authors.affiliation: Division of Thoracic Surgery, Taipei Veterans General Hospital; Institute of Emergency and Critical Care Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Han-Shui
authors.initials: HS
authors.lastname: Hsu
authors.affiliation: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan. wwlai@mail.ncku.edu.tw.
authors.forename: Wu-Wei
authors.initials: WW
authors.lastname: Lai
authors.affiliation: Department of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. ycw5798@mail.ncku.edu.tw.|Department of Pharmacology and Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, Taiwan. ycw5798@mail.ncku.edu.tw.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000368:Aged; D044466:Asian People; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015996:Survival Rate; D013624:Taiwan; D044465:White People
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: DNA methylation array; Lung adenocarcinoma; Prognosis; Pyrosequencing; Risk score