外周血ctDNA中PCDH8和PCDH17基因甲基化在高级别浆液性卵巢癌筛查和预后中的临床价值-东南大学学报医学版

外周血ctDNA中PCDH8和PCDH17基因甲基化在高级别浆液性卵巢癌筛查和预后中的临床价值

单位：1. 自贡市第一人民医院妇产科, 四川自贡 643000;
2. 重庆医科大学附属第二人民医院妇产科, 重庆 400010

关键词：循环肿瘤DNA 原钙黏蛋白8 原钙黏蛋白17 高级别浆液性卵巢癌表观遗传学

分类号：R737.31

出版年·卷·期（页码）：2022·41·第三期（394-401）

摘要：

目的：探讨外周血循环肿瘤DNA（ctDNA）中原钙黏蛋白（PCDH）8和PCDH17基因甲基化在高级别浆液性卵巢癌（HGSOC）筛查和预后中的临床价值。方法：选取2016年7月至2018年7月在自贡市第一人民医院诊治并接受手术治疗的85例HGSOC患者（HGSOC组）和35例非恶性诊断患者（对照组）作为研究对象，收集手术组织标本和诊断时的血液样本。采用甲基化荧光（MethyLight）定量分析组织和ctDNA中PCDH8、PCDH17基因甲基化水平，以甲基化百分比参数（PMR）表示。随访截至2021年7月，记录复发时间。结果：HGSOC组肿瘤组织和ctDNA中PCDH8、PCDH17基因PMR值高于对照组（P<0.05），且HGSOC组肿瘤组织与ctDNA中PCDH8基因PMR值、PCDH17基因PMR值均呈正相关（r_s分别为0.465、0.432，均P<0.001）。ctDNA中PCDH8和PCDH17基因PMR值联合用于筛查HGSOC的曲线下面积（AUC）为0.857（95%CI 0.785~0.929），灵敏度和特异度分别为83.5%、80.0%。PCDH8、PCDH17基因甲基化与FIGO分期、血清CA-125水平、肿瘤直径有关（P<0.05）。经多因素Cox比例风险回归模型分析，外周血ctDNA中PCDH8和PCDH17基因甲基化是HGSOC患者术后复发的独立预测因子（P<0.05）。结论：外周血ctDNA中PCDH8、PCDH17基因甲基化检测可以作为HGSOC筛查或预测肿瘤术后进展的潜在的生物标志物。

Objective: To investigate the clinical value of methylation of protocadherin(PCDH) 8 and PCDH17 genes in peripheral blood circulating tumor DNA(DNA) in screening and predicting high-grade serous ovarian cancer(HGSOC). Methods: 85 patients with HGSOC(HGSOC group) and 35 patients with non-malignant diagnosis(control group) were selected from July 2016 to July 2018. Surgical tissue samples and diagnostic blood samples were collected. The methylation levels of PCDH8 and PCDH17 genes in ctDNA and tissues were measured by MethyLight quantitative analysis and expressed by percent of methylated reference(PMR). The follow up was up to July 2021 and the time of recurrence was recorded. Results: The PMR values of PCDH8 and PCDH17 in ctDNA or tissues of HGSOC group were both higher than those in the control group(P<0.05), and the PMR values of PCDH8 or PCDH17 in HGSOC tissues and ctDNA were both positively correlated(r_s=0.465, 0.432, all P<0.001). The area under ROC curve of combined PMR value of PCDH8 and PCDH17 gene in ctDNA for screening HGSOC was 0.857(95%CI:0.785-0.929), and the sensitivity and specificity were 83.5% and 80.0%, respectively. The methylation of PCDH8 and PCDH17 genes was associated with FIGO stage, serum CA-125 level and tumor diameter(P<0.05). Multivariate Cox proportional hazard regression model analysis showed that hypermethylation of PCDH8 or PCDH17 genes in peripheral blood ctDNA were the independent predictors of postoperative recurrence in patients with HGSOC(P<0.05). Conclusion: The methylation detection of PCDH8 and PCDH17 genes in peripheral blood ctDNA can be used as potential biomarkers for HGSOC screening or predicting the tumor progression after surgery.

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