Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking

Qiang Tan, Guan Wang, Jia Huang, Zhengping Ding, Qingquan Luo, Tony Mok, Qian Tao, Shun Lu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The importance of epigenetic regulation has been increasingly recognized in the development of cancer. In this study, we investigated the impact of smoking, a major risk factor of lung cancer, on DNA methylation by comparing the genome-wide DNA methylation patterns between lung adenocarcinoma samples from six smokers and six nonsmokers. We identified that smoking-induced DNA methylations were enriched in the calcium signaling and neuroactive ligand receptor signaling pathways, which are closely related to smoking-induced lung cancers. Interestingly, we discovered that two genes in the mitogen-activated protein kinase signaling pathway (RPS6KA3 and ARAF) were hypomethylated in smokers but not in nonsmokers. In addition, we found that the smoking-induced lung cancer-specific DNA methylations were mostly enriched in nuclear activities, including regulation of gene expression and chromatin remodeling. Moreover, the smoking-induced hypermethylation could only be seen in lung adenocarcinoma tissue but not in adjacent normal lung tissue. We also used differentially methylated DNA loci to construct a diagnostic model to distinguish smoking-associated lung cancer from nonsmoking lung cancer with a sensitivity of 88.9% and specificity of 83.2%. Our results provided novel evidence to support that smoking can cause dramatic changes in the DNA methylation landscape of lung cancer, suggesting that epigenetic regulation of specific oncogenic signaling pathways plays an important role in the development of lung cancer.

Original languageEnglish (US)
Pages (from-to)1471-1479
Number of pages9
JournalOncoTargets and Therapy
Volume6
DOIs
StatePublished - Nov 13 2013

Fingerprint

DNA Methylation
Epigenomics
Lung Neoplasms
Smoking
Chromatin Assembly and Disassembly
Calcium Signaling
Adenocarcinoma of lung
Gene Expression Regulation
Mitogen-Activated Protein Kinases
Genome
Ligands
Sensitivity and Specificity
Lung
DNA
Genes

Keywords

  • Epigenome
  • Lung cancer
  • Methylation
  • Smoking
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking. / Tan, Qiang; Wang, Guan; Huang, Jia; Ding, Zhengping; Luo, Qingquan; Mok, Tony; Tao, Qian; Lu, Shun.

In: OncoTargets and Therapy, Vol. 6, 13.11.2013, p. 1471-1479.

Research output: Contribution to journalArticle

Tan, Qiang ; Wang, Guan ; Huang, Jia ; Ding, Zhengping ; Luo, Qingquan ; Mok, Tony ; Tao, Qian ; Lu, Shun. / Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking. In: OncoTargets and Therapy. 2013 ; Vol. 6. pp. 1471-1479.
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