Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma

被引：56

作者：

Daugaard, Iben ^{[1
]}

Dominguez, Diana ^{[1
]}

Kjeldsen, Tina E. ^{[1
]}

Kristensen, Lasse S. ^{[1
]}

Hager, Henrik ^{[2
]}

Wojdacz, Tomasz K. ^{[1
,3
]}

Hansen, Lise Lotte ^{[1
]}

机构：

[1] Aarhus Univ, Dept Biomed, Bartholins Alle 6, DK-8000 Aarhus C, Denmark

[2] Aarhus Univ Hosp, Dept Pathol, Norrebrogade 45, DK-8000 Aarhus C, Denmark

[3] Aarhus Inst Adv Studies, Hoegh Guldbergs Gade 6B, DK-8000 Aarhus C, Denmark

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

DNA METHYLATION BIOMARKERS; TUMOR-SUPPRESSOR GENE; GENOME-WIDE ANALYSIS; CPG ISLAND; CANCER; BREAST; HYPERMETHYLATION; ASSOCIATION; STATISTICS;

D O I：

10.1038/srep35807

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Lung cancer is the number one cause of cancer-related deaths worldwide. DNA methylation is an epigenetic mechanism that regulates gene expression, and disease-specific methylation changes can be targeted as biomarkers. We have compared the genome-wide methylation pattern in tumor and tumor-adjacent normal lung tissue from four lung adenocarcinoma (LAC) patients using DNA methylation microarrays and identified 74 differentially methylated regions (DMRs). Eighteen DMRs were selected for validation in a cohort comprising primary tumors from 52 LAC patients and tumor-adjacent normal lung tissue from 32 patients by methylation-sensitive high resolution melting (MS-HRM) analysis. Significant increases in methylation were confirmed for 15 DMRs associated with the genes and genomic regions: OSR1, SIM1, GHSR, OTX2, LOC648987, HIST1H3E, HIST1H3G/HIST1H2BI, HIST1H2AJ/HIST1H2BM, HOXD10, HOXD3, HOXB3/HOXB4, HOXA3, HOXA5, Chr1(q21.1). A, and Chr6(p22.1). In particular the OSR1, SIM1 and HOXB3/HOXB4 regions demonstrated high potential as biomarkers in LAC. For OSR1, hypermethylation was detected in 47/48 LAC cases compared to 1/31 tumor-adjacent normal lung samples. Similarly, 45/49 and 36/48 LAC cases compared to 3/31 and 0/31 tumor-adjacent normal lung samples showed hypermethylation of the SIM1 and HOXB3/HOXB4 regions, respectively. In conclusion, this study has identified and validated 15 DMRs that can be targeted as biomarkers in LAC.

引用

页数：11

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