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首页> 外文期刊>Epigenetics & Chromatin >DNA methylation markers for disease progression and survival in Barrett’s Esophagus
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DNA methylation markers for disease progression and survival in Barrett’s Esophagus

机译：DNA甲基化标记物用于Barrett食管的疾病进展和生存

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Esophageal adenocarcinoma (EAC), with its precursorlesion Barrett’s esophagus (BE), accounts for 2% of allcancer-related deaths and has a very poor prognosis witha median survival of less than one year. In addition, theprevalence of BE is rapidly rising in the Western World,resulting in a large number of individuals “at risk” forthis disease. However, a major limitation for defining thisrisk population is the absence of reliable biomarkers,which also affects the development of surveillance strategiesand chemoprevention therapies for BE and EAC.The development of BE has been thought to arise largelybecause of chronic esophageal inflammation and the subsequentthe expansion of some sort of an altered stemcell population due to alteration of stromal niche factors.This also leads to epigenetic alterations, which are commonin cancer initiation and progression, such aschanges in DNA methylation. Many genes show greatpromise as specific DNA methylation biomarkers, whichoffer several advantages, as they are easy accessible inbody fluids such as blood, sputum, or urine and the DNAcontaining the methylation information can be isolatedfrom formalin fixed paraffin embedded (FFPE) tissue aswell; the positive methylation signal can also be detectedin the presence of huge amounts of material from normalcells giving a negative signal. We measured two DNAmethylation markers, DKK1 (a WNT antagonist, knownto be methylated in colorectal and gastric cancer whichhas a function tumor cell niche formation) and TFAP2E(a novel biomarker for nonresponse towards 5FU incolon cancer) in a retrospective cohort of patients withEAC collected at the Institute of Pathology at the TUMunich (FFPE material), using Methylspecific-HRM-PCRfollowed by pyrosequencing.ResultsIn a cohort of 60 EAC patients (primary resections), DKK1methylation was associated with overall survival (ROCanalysis, AUC 0.69, 95% CI, p < 0,001) as well as diseasefree survival (AUC 0.63, 95% CI, p < 0,01). In anothercohort of 55 patients who received neoadjuvant chemotherapy(5FU, cisplatin, folinic acid) TFAP2E methylationwas found also to be associated with overall survival(AUC 0.64, 95% CI, p < 0,05) but less so if patients whodid not receive 5FU (taxol, cisplatin) were included (AUC0.62,95% CI, p < 0,05).
机译：食管腺癌（EAC）以巴雷特（Barrett）食道（BE）为先驱，占所有与癌症相关的死亡的2％，并且预后很差，中位生存期不到一年。此外，在西方世界，BE的患病率迅速上升，导致大量个体“处于危险之中”。然而，定义该风险人群的主要限制是缺乏可靠的生物标记物，这也影响了BE和EAC的监测策略和化学预防疗法的发展。人们认为BE的发展主要是由于慢性食管炎症和随后的食管扩张引起的。由于基质小生境因子的改变而导致干细胞种群发生某种改变，这也导致表观遗传改变，这在癌症的发生和发展中很常见，例如DNA甲基化的改变。许多基因作为特定的DNA甲基化生物标记物显示出了巨大的前景，这具有许多优势，因为它们很容易在体液（例如血液，痰液或尿液）中获取，并且还可以从福尔马林固定石蜡包埋（FFPE）组织中分离出含有甲基化信息的DNA;在存在来自正常细胞的大量物质的情况下，也可以检测到正甲基化信号，从而给出负信号。我们在回顾性队列研究中收集了两种DNA甲基化标记物DKK1（一种WNT拮抗剂，已知在大肠癌和胃癌中具有甲基化作用，它具有肿瘤细胞生态位形成的功能）和TFAP2E（一种对5FU结肠癌无反应的新型生物标记物）。结果在60例EAC患者（初次切除）中，DKK1甲基化与总体生存率相关（ROCanalysis，AUC 0.69，95％CI，p <0.001）和无病生存期（AUC 0.63，95％CI，p <0.01）。在另一组55例接受新辅助化疗（5FU，顺铂，亚叶酸）的患者中，TFAP2E甲基化也与总体生存率相关（AUC 0.64，95％CI，p <0.05），而如果不接受5FU的患者则较少（紫杉醇，顺铂）包括在内（AUC0.62,95％CI，p <0.05）。

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