國家衛生研究院 NHRI:Item 3990099045/8422
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    题名: Clinical relevance of plasma DNA methylation in colorectal cancer patients identified by using a genome-wide high-resolution array
    作者: Lin, PC;Lin, JK;Lin, CH;Lin, HH;Yang, SH;Jiang, JK;Chen, WS;Chou, CC;Tsai, SF;Chang, SC
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: Background: DNA methylationis 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.
    日期: 2015-12
    關聯: Annals of Surgical Oncology. 2015 Dec;22(Suppl. 3):1419-1427.
    Link to: http://dx.doi.org/10.1245/s10434-014-4277-2
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1068-9265&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000412846400004
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84952875135
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