DNA Methylation of LRRC3B: A Biomarker for Survival of Early-Stage Non-Small Cell Lung Cancer Patients

Details

• Personal Author:
  Bjaanæs MM ; Christiani, David C. ; Esteller M ; Fleischer T ; Guo Y ; Helland Å ; Karlsson A ; Planck M ; Salama SM ; Shen S ; Staaf J ; Su L ; Wei Y ; Zhang R ; Zhu Z
• Description:
  Background: Previous studies support a tumor-suppressor role for LRRC3B across various types of cancers. We aimed to investigate the association between DNA methylation of LRRC3B and overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC). Methods: This study included 1,230 patients with early-stage NSCLC. DNA was extracted from lung tumor tissues and DNA methylation was measured using Illumina Infinium HumanMethylation450 BeadChips. The association between DNA methylation and OS was first tested using Cox regression on a discovery cohort and then validated in an independent cohort. Next, the association between DNA methylation and gene expression was investigated in two independent cohorts. Finally, the association between gene expression and OS was investigated in three independent groups of patients. Results: Three novel DNA methylation sites in LRRC3B were significantly associated with OS in two groups of patients. Patients with hypermethylation in the DNA methylation sites had significantly longer survival than the others in both the discovery cohort (HR, 0.62; P = 2.02 × 10-05) and validation cohort (HR, 0.55; P = 4.44 × 10-04). The three DNA methylation sites were significantly associated with LRRC3B expression, which was also associated with OS. Conclusions: Using clinical data from a large population, we illustrated the association between DNA methylation of LRRC3B and OS of early-stage NSCLC. Impact: We provide evidence of plausibility for building biomarkers on DNA methylation of LRRC3B for OS of early-stage NSCLC, thus filling a gap between previous in vitro studies and clinical applications. [Description provided by NIOSH]
• Subjects:
  Biomarkers Cohort Studies Genetics Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Cancer Cancer Survivors Cohort Studies Deoxyribonucleic Acids DNA Gene Expression Genes Lung Cancer Survival Rate Tumor Inhibition
• ISSN:
  1055-9965
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  27
• Issue:
  12
• NIOSHTIC Number:
  nn:20055802
• Citation:
  Cancer Epidemiol Biomark Prev 2018 Dec; 27(12):1527-1535
• Contact Point Address:
  David C. Christiani, Harvard School of Public Health, Building I, Room 1407, 665 Huntington Avenue, Boston, MA 02115
• Email:
  dchris@hsph.harvard.edu
• Federal Fiscal Year:
  2019
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Cancer Epidemiology, Biomarkers & Prevention
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2119a0f21c108e844cce60f14d61f77cf8d96a044e88c413f5ad0e9b65a84539fadc14fc7a51e5babbae358192879281257ca559fe68735e18a0af4653e39068
• Download URL:
  https://stacks.cdc.gov/view/cdc/213571/cdc_213571_DS1.pdf
• File Type:
  [PDF - 1.34 MB ]