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Identification of smoking relevant DNA methylation alteration and long non-coding RNA in lung adenocarcinoma : Discovery analysis across TCGA data and validation in Korean patients

폐선암종에서 흡연 연관 DNA methylation 변이와 후성유전조절 long non-coding RNA 발굴 연구 ;공공빅데이터 활용과 한국인 폐암환자 검증

  • 안상정 (대학원 의학과 병리학전공)

초록/요약

In this study, we aimed to explore the epigenetic regulated long noncoding RNA (lncRNA) and DNA methylation in lung adenocarcinoma (LUAD). TCGA downloaded from Gene Expression Omnibus included a DNA methylation dataset and an mRNA expression profiles dataset, both of which included 184 LUAD tissue samples and 21 adjacent normal lung tissue samples. LUAD samples were divided into smoker LUAD and never-smoker LUAD. The differentially methylated regions (DMRs) were screened by negative correlation with expression level of mRNA in smoker LUAD vs. normal, never-smoker LUAD vs. normal, and smoker LUAD vs. never smoker LUAD. The differentially expressed lncRNAs (DE-lncRNAs) were determined in each groups. Among DE-lncRNAs, IPA-mapped candidate lncRNAs were concerned. Integrated analysis of DE-lncRNAs associated with DNA methylation was determined using IPA. Bisulfite sequencing was used to validate the final DMRs from smoker LUAD vs. normal and smoker LUAD vs. never-smoker LUAD comparisons in 76 patients. The annotation result of their DMRs and DE-lncRNAs in smoker LUAD vs. never-smoker LUAD comparison showed that the most significantly related category of GO analysis was LPS/IL-1 Mediated Inhibition of RXR Function. Our study indicated that epigenetic regulated lncRNAs were significantly and differentially expressed in smoker LUAD vs. never-smoker LUAD and in smoker LUAD vs. normal comparison. They may exert a significant epigenetic role in lung cancer development and could be potential targets for future treatment of LUAD.

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목차

ABSTRACT 5
INTRODUCTION 6
MATERIAL AND METHOD 9
RESULT 12
DISCUSSION 14
TABLES 18
FIGURES 28
REFERENCES 38

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