Department of Gynecology, People's Hospital of Mianzhu City, Deyang, Sichuan, China.
College of Medical Technology, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
PLoS One. 2021 Apr 26;16(4):e0250717. doi: 10.1371/journal.pone.0250717. eCollection 2021.
Ovarian cancer (OC) is a leading cause of death in gynecological malignancies worldwide. Multitudinous studies have suggested the potential of circulating tumor DNA (ctDNA), circulating microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as novel diagnostic molecular biomarkers for OC. Here, we include three updated meta-analysis methods using different molecular biomarkers to evaluate their discriminative value in OC diagnosis.
We conducted three meta-analyses after searching different databases, and 23 eligible articles, including 8 concerning ctDNA, 11 concerning miRNAs, and 4 concerning lncRNAs, were found. Further, we pooled data concerning the sensitivity, specificity, and other indicators of accuracy for ctDNA/miRNAs/lncRNAs in the diagnosis of OC. The heterogeneity was further explored by meta-regressions and subgroup analyses, and Deeks' funnel plots were used to measure the publication bias of these three meta-analyses.
In all, this meta-analysis included 1732 OC patients and 3958 controls. The sensitivity of ctDNA for OC diagnosis was superior to that of lncRNA and miRNA (84% vs. 81% vs. 78%). Moreover, the specificity and area under the receiver-operating characteristic (ROC) curve (AUC) of ctDNA were 91% and 94%, which were significantly higher than those of miRNA and lncRNAs (78% and 85%; 78% and 86%, respectively). No significant difference was observed among the two meta-analyses of ctDNA and lncRNA (P > 0.05) with regard to publication bias, while the meta-analysis of miRNA observed a significantly small publication bias (P < 0.05).
ctDNA/miRNAs/lncRNAs may be promising molecular biomarkers for OC diagnosis. Further large-scale studies are needed to verify the potential applicability of ctDNA/miRNAs/lncRNAs molecular signatures alone or in combination as diagnostic molecular biomarkers for OC.
卵巢癌（OC）是全球妇科恶性肿瘤死亡的主要原因。众多研究表明，循环肿瘤 DNA（ctDNA）、循环 microRNAs（miRNAs）和长非编码 RNA（lncRNAs）作为 OC 的新型诊断分子生物标志物具有潜在价值。在这里，我们纳入了三种使用不同分子生物标志物的更新元分析方法，以评估它们在 OC 诊断中的区分价值。
我们在不同数据库中进行了三次元分析，共找到了 23 篇符合条件的文章，其中 8 篇涉及 ctDNA，11 篇涉及 miRNAs，4 篇涉及 lncRNAs。此外，我们汇总了关于 ctDNA/miRNAs/lncRNAs 用于 OC 诊断的敏感性、特异性和其他准确性指标的数据。通过元回归和亚组分析进一步探讨了异质性，并使用 Deeks 漏斗图评估了这三种元分析的发表偏倚。
本元分析共纳入 1732 例 OC 患者和 3958 例对照。ctDNA 用于 OC 诊断的敏感性优于 lncRNA 和 miRNA（84% 对 81% 对 78%）。此外，ctDNA 的特异性和受试者工作特征（ROC）曲线下面积（AUC）分别为 91%和 94%，显著高于 miRNA 和 lncRNA（78%和 85%；78%和 86%）。ctDNA 和 lncRNA 的两个元分析在发表偏倚方面无显著差异（P > 0.05），而 miRNA 的元分析则观察到显著的小发表偏倚（P < 0.05）。
ctDNA/miRNAs/lncRNAs 可能是 OC 诊断有前途的分子生物标志物。需要进一步的大规模研究来验证 ctDNA/miRNAs/lncRNAs 分子特征作为 OC 诊断分子生物标志物的潜在适用性，无论是单独使用还是联合使用。
