Schott Sarah, Yang Rongxi, Stöcker Sarah, Canzian Federico, Giese Nathalia, Bugert Peter, Bergmann Frank, Strobel Oliver, Hackert Thilo, Sohn Christof, Burwinkel Barbara
Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, 69120 Heidelberg, Germany.
Department of Gynecology and Obstetrics, University Women's Clinic, 69120 Heidelberg, Germany.
Oncotarget. 2017 Jun 27;8(40):67614-67625. doi: 10.18632/oncotarget.18757. eCollection 2017 Sep 15.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy which is mostly diagnosed in advanced and inoperable stages though surgery remains the only curable therapeutic approach. Early detection markers are urgently needed to improve diagnosis. Altered hyaluronoglucosaminidase 2 gene () DNA methylation in peripheral blood is known to be associated with malignancy at early stage but has not been evaluated in PDAC patients. This study evaluates the association between blood-based methylation and PDAC by a case-control study with 191 controls and 82 PDAC patients. Decreased methylation of all four investigated methylation sites showed highly significant association with PDAC (odds ratio (ORs) per -10% methylation ranging from 2.03 to 12.74, depending on the specific CpG site, 0.0001 for all). methylation sites were also distinguishable between stage I&II PDAC (61 subjects) and controls (ORs per-10% methylation from 3.17 - 23.04, 0.0001 for all). Thus, methylation level enabled a very good discrimination of PDAC cases from healthy controls (area under curve (AUC) = 0.92, 95% Confidence interval (C.I.): 0.88 - 0.96), and was also powerful for the detection of PDAC at stage I&II (AUC = 0.93, 95% C.I.: 0.89 - 0.98). Moreover, the blood-based methylation pattern was similar among PDAC patients with differential clinical characteristics, and showed no correlation with the overall survival of PDAC patients. Our study reveals a strong association between decreased methylation in peripheral blood and PDAC, and provides a promising blood-based marker for the detection of PDAC.
胰腺导管腺癌（PDAC）是一种极具致死性的恶性肿瘤，尽管手术仍然是唯一可治愈的治疗方法，但大多数患者在疾病晚期才被诊断出来，此时已无法进行手术。迫切需要早期检测标志物来改善诊断。已知外周血中透明质酸葡萄糖胺酶2基因（）的DNA甲基化改变与早期恶性肿瘤有关，但尚未在PDAC患者中进行评估。本研究通过一项病例对照研究，纳入191名对照者和82名PDAC患者，评估基于血液的甲基化与PDAC之间的关联。所有四个研究的甲基化位点的甲基化水平降低均与PDAC呈高度显著相关性（每降低10%甲基化的优势比（OR）范围为2.03至12.74，具体取决于特定的CpG位点，所有位点的P<0.0001）。甲基化位点在I&II期PDAC患者（61名受试者）和对照者之间也有显著差异（每降低10%甲基化的OR为3.17至23.04，所有位点的P<0.0001）。因此，甲基化水平能够很好地区分PDAC病例与健康对照者（曲线下面积（AUC）=0.92，95%置信区间（C.I.）：0.88 - 0.96），并且对于检测I&II期PDAC也很有效（AUC = 0.93，95% C.I.：0.89 - 0.98）。此外，具有不同临床特征的PDAC患者之间基于血液的甲基化模式相似，并且与PDAC患者的总生存期无关。我们的研究揭示了外周血中甲基化水平降低与PDAC之间存在密切关联，并为PDAC的检测提供了一种有前景的基于血液的标志物。
