Clinical Relevance of Plasma DNA Methylation in Colorectal Cancer Patients Identified by Using a Genome-Wide High-Resolution Array

Pei Ching Lin, Jen Kou Lin, Chien Hsing Lin, Hung Hsin Lin, Shung Haur Yang, Jeng Kai Jiang, Wei Shone Chen, Chih Chi Chou, Shih Feng Tsai, Shih Ching Chang*

*此作品的通信作者

研究成果: Article同行評審

37 引文 斯高帕斯(Scopus)

摘要

Background: DNA methylation is a potential tumor marker for several cancers, including colorectal cancer (CRC), because of its heritable and stable characteristics. Methods: Using a high-resolution, genome-wide approach, we epigenotyped >450,000 CpG sites in tumor and adjacent non-tumor tissues from 23 microsatellite instability (MSI)/microsatellite stability (MSS) CRC cases. Using matrix-assisted laser desorption ionization–time of flight mass spectrometry, the methylation status of five frequently hypermethylated genes were confirmed in 75 independent CRC series and 353 CRC patients with available plasma. Results: Compared with non-tumor tissues, 13 MSI tumors had 34,836 (7 %) aberrant methylation sites, 87 % of which were hypermethylated. In contrast, only 9,806 (2 %) differentially methylated sites were identified in ten MSS cases (62 % hypermethylated). In both MSI and MSS, 228 promoter-associated CpG islands were hypermethylated, with AGBL4, ZNF625, MDFI, TWIST1, and FLI1 being most frequently hypermethylated. In an independent set of 35 MSI and 40 MSS cases, the methylation status of these five genes significantly differed between tumor and adjacent non-tumor tissues. Of 353 CRC patients, 230 (65.2 %), 232 (65.7 %), and 247 (70.0 %) had AGBL4, FLI1, and TWIST1 promoter hypermethylation in circulating cell-free DNA, respectively. In patients without metastasis, the sensitivity of any two or three hypermethylation markers was 52.8–57.8 and 27.9–38.9 %, respectively. The sensitivity of any two or three markers was significantly high in patients with stage IV disease (73.0 and 55.6 %, respectively). The prognostic value of these epimarkers was inconclusive. Conclusion: DNA methylation patterns differed in CRC subtypes. The identified hypermethylation markers in CRC patients may have good sensitivity in different CRC stages.

原文English
頁(從 - 到)1419-1427
頁數9
期刊Annals of Surgical Oncology
22
DOIs
出版狀態Published - 1 12月 2015

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