诊断为上皮性卵巢癌(OC)的患者的5年生存率为49%。对于早期疾病,5年生存率在90%以上。然而,晚期疾病占大多数病例,因为早期患者通常无症状或存在非特异性症状,强调需要诊断工具进行早期诊断。液体活检是一种最小侵入性的基于血液的方法,利用从肿瘤细胞脱落的循环肿瘤DNA(ctDNA)实时检测肿瘤遗传学和表观遗传学。启动子区域的DNA甲基化增加是肿瘤发生过程中的早期事件。甲基化可以在ctDNA中检测到,强调甲基化ctDNA作为OC诊断的生物标志物的前景。许多研究已经研究了来自血浆或血清的ctDNA中的多种甲基化生物标志物,用于区分OC患者与卵巢良性疾病患者和/或健康女性。本系统综述总结并评估了目前研究的DNA甲基化生物标志物在血液来源的ctDNA中用于早期诊断OC的性能。系统地搜索了PubMed的MEDLINE和Elsevier的Embase,以及重要的结果,如OC病例和对照的甲基化频率,绩效指标,以及分析前因素被提取出来。总的来说,29项研究符合本系统综述的纳入标准。甲基化分析最常用的方法是甲基化特异性PCR,一半的研究使用血浆,另一半使用血清。RASSF1A,BRCA1和OPCML是研究最多的基因特异性甲基化生物标志物,OPCML具有最佳的性能度量。一般来说,甲基化面板表现优于单基因特异性甲基化生物标志物,一个甲基化组的103,456个不同区域和1,116,720个CpG在训练和验证队列中具有更好的性能。然而,证据仍然有限,和有希望的甲基化面板,以及本综述中强调的基因特异性甲基化生物标志物,需要大的验证,与早期无症状OC患者的前瞻性队列,以评估临床环境中的真正诊断价值。
Patients diagnosed with epithelial ovarian cancer (OC) have a 5-year survival rate of 49%. For early-stage disease, the 5-year survival rate is above 90%. However, advanced-stage disease accounts for most cases as patients with early stages often are asymptomatic or present with unspecific symptoms, highlighting the need for diagnostic tools for early diagnosis. Liquid biopsy is a minimal invasive blood-based approach that utilizes circulating tumor DNA (ctDNA) shed from tumor cells for real-time detection of tumor genetics and epigenetics. Increased DNA methylation of promoter regions is an early event during tumorigenesis, and the methylation can be detected in ctDNA, accentuating the promise of methylated ctDNA as a biomarker for OC diagnosis. Many studies have investigated multiple methylation biomarkers in ctDNA from plasma or serum for discriminating OC patients from patients with benign diseases of the ovaries and/or healthy females. This systematic
review summarizes and evaluates the performance of the currently investigated DNA methylation biomarkers in blood-derived ctDNA for early diagnosis of OC. PubMed\'s MEDLINE and Elsevier\'s Embase were systematically searched, and essential results such as methylation frequency of OC cases and controls, performance measures, as well as preanalytical factors were extracted. Overall, 29 studies met the inclusion criteria for this systematic
review. The most common method used for methylation analysis was methylation-specific PCR, with half of the studies using plasma and the other half using serum. RASSF1A, BRCA1, and OPCML were the most investigated gene-specific methylation biomarkers, with OPCML having the best performance measures. Generally, methylation panels performed better than single gene-specific methylation biomarkers, with one methylation panel of 103,456 distinct regions and 1,116,720 CpGs having better performance in both training and validation cohorts. However, the evidence is still limited, and the promising methylation panels, as well as gene-specific methylation biomarkers highlighted in this
review, need validation in large, prospective cohorts with early-stage asymptomatic OC patients to assess the true diagnostic value in a clinical setting.