循环游离 DNA 在卵巢癌中的诊断意义评估：一项更新的荟萃分析。

Diagnostic significance assessment of the circulating cell-free DNA in ovarian cancer: An updated meta-analysis.

机构信息

The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, China; Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, China.

The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, China; Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou 730000, China; Key laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou 730000, China.

出版信息

Gene. 2019 Sep 25;714:143993. doi: 10.1016/j.gene.2019.143993. Epub 2019 Jul 19.

DOI:10.1016/j.gene.2019.143993

PMID:31330238

Abstract

BACKGROUND

Recently, disagreements remain in increasing evidence about the potential value of circulating cell-free DNA (cfDNA) as a noninvasive diagnostic biomarker for ovarian cancer (OC). Here, this update meta-analysis was performed to further assess the diagnostic performance of circulating cfDNA in discriminating OC from non-cancerous individuals.

METHODS

We performed a systemic literature search of PubMed, Embase, Web of Science, Cochrane Library, OVID, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases to obtain 22 eligible articles including a total of 1125 patients and 1244 controls. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and area under receiver operating characteristics curves (AUROC) of the included studies for cfDNA in diagnosing OC patients were used to estimate the diagnostic value. The clinical utility of cfDNA was evaluated by Fagan nomogram. Heterogeneity was explored utilizing subgroup analysis and meta-regression.

RESULTS

The pooled sensitivity and specificity were 73% and 90%, the DOR and AUROC were 25.29 and 0.90, respectively. Subgroup analyses and meta-regression, according to patients' region, study design, clinical stage, specimen types, detection indicators, simple size, publication year revealed there were no significant sources of heterogeneity. Additionally, subgroup analyses showed qualitative detection (methylation detection); TNM stage I-IV, publication year 2011-2018, serum-based cfDNA assays exhibited better diagnostic performance as compared to quantitative detection, TNM stage III-IV, publication year 2002-2010; plasma-based cfDNA assays, and more participants and prospective studies manifested superior diagnostic accuracy. The result of sensitivity analysis indicated no study exclusively contributed to the heterogeneity and Deeks' funnel plot suggested no evidence of significant publication bias.

CONCLUSIONS

Our meta-analysis found the qualitative detection (methylation); TNM stage I-IV, publication year 2011-2018 were related to more effective diagnostic accuracy for OC. However, serum-based cell-free DNA detection should be cautiously interpreted due to unclear factors. Hence, further large-scale longitudinal studies are required to validate the diagnostic potential of cell-free DNA. The present study provides to accrue knowledge of cell-free DNA levels for future researches.

摘要

背景

最近，关于循环游离 DNA（cfDNA）作为卵巢癌（OC）非侵入性诊断生物标志物的潜在价值的证据越来越多，但仍存在分歧。在这里，进行了更新的荟萃分析，以进一步评估循环 cfDNA 区分 OC 患者与非癌症个体的诊断性能。

方法

我们对 PubMed、Embase、Web of Science、Cochrane 图书馆、OVID、中国国家知识基础设施（CNKI）和万方数据库进行了系统的文献检索，以获得 22 篇符合条件的文章，其中包括 1125 名患者和 1244 名对照。使用包含研究的 cfDNA 诊断 OC 患者的汇总敏感性、特异性、诊断优势比（DOR）和受试者工作特征曲线下面积（AUROC）来估计诊断价值。使用 Fagan 列线图评估 cfDNA 的临床实用性。通过亚组分析和荟萃回归探索异质性。

结果

汇总敏感性和特异性分别为 73%和 90%，DOR 和 AUROC 分别为 25.29 和 0.90。根据患者所在地区、研究设计、临床分期、标本类型、检测指标、样本量大小、发表年份进行亚组分析和荟萃回归，结果显示无明显异质性来源。此外，亚组分析显示，定性检测（甲基化检测）；TNM 分期 I-IV 期，发表年份为 2011-2018 年，与定量检测、TNM 分期 III-IV 期，发表年份为 2002-2010 年相比，血清 cfDNA 检测具有更好的诊断性能；血浆 cfDNA 检测和更多的参与者和前瞻性研究表现出更高的诊断准确性。敏感性分析的结果表明，没有研究专门导致异质性，Deeks 漏斗图表明没有明显的发表偏倚证据。

结论

本荟萃分析发现，定性检测（甲基化）；TNM 分期 I-IV 期，发表年份为 2011-2018 年与 OC 更有效的诊断准确性有关。然而，由于存在不明因素，应谨慎解释基于血清的游离细胞 DNA 检测。因此，需要进一步开展大规模的纵向研究来验证游离 DNA 的诊断潜力。本研究为未来的研究提供了对游离 DNA 水平的认识。