1 First Faculty of Medicine, Institute of Biology and Medical Genetics, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
2 Institute of Pathology, University Hospital Brno, Brno, Czech Republic.
Reprod Sci. 2019 Apr;26(4):510-522. doi: 10.1177/1933719118776808. Epub 2018 May 20.
Ovarian cancer as the most fatal gynecological malignancy is often manifested by excessive fluid accumulation known as ascites or effusion. Ascites-derived microRNAs (miRNAs) may be closely associated with ovarian cancer progression. However, our knowledge of their roles, altered expression, and clinical outcomes remained limited. In this study, large-scale expression profiling of 754 human miRNAs was performed using real-time quantitative polymerase chain reaction and 384-well TaqMan array human miRNA A and B cards to identify differentially expressed miRNAs between extracellular fraction of the ascitic fluid associated with high-grade serous ovarian carcinomas and control plasma. Of the 754 miRNAs, 153 were significantly differentially expressed relative to the controls. Expression of 7 individual miRNAs (miR-200a, miR-200b, miR-200c, miR-141, miR-429, miR-1290, and miR-30a-5p) was further validated in extended sample sets, including serous, endometrioid, and mucinous subtypes. All miR-200 family members and miR-1290 were conspicuously overexpressed, while miR-30a-5p was only weakly overexpressed. The ability of miRNAs expression to discriminate the pathological samples from the controls was strong. Receiver operating characteristic curve analyses found area under the curve (AUC) values of 1.000 for miR-200a, miR-200c, miR-141, miR-429, and miR-1290 and of AUC 0.996 and 0.885 for miR-200b and miR-30a-5p, respectively. Preliminary survival analyses indicated low expression level of miR-200b as significantly related to longer overall survival (hazard ratio [HR]: 0.25, mean survival 44 months), while high expression level was related to poor overall survival (HR: 4.04, mean survival 24 months). Our findings suggested that ascites-derived miRNAs should be further explored and evaluated as potential diagnostic and prognostic biomarkers for ovarian cancer.
卵巢癌是最致命的妇科恶性肿瘤之一，常表现为过度液体积聚，称为腹水或渗出液。腹水来源的 microRNAs（miRNAs）可能与卵巢癌的进展密切相关。然而，我们对它们的作用、表达改变和临床结局的认识仍然有限。在这项研究中，使用实时定量聚合酶链反应和 384 孔 TaqMan 阵列人类 miRNA A 和 B 卡对 754 个人类 miRNAs 进行了大规模表达谱分析，以鉴定与高级别浆液性卵巢癌相关的腹水细胞外部分与对照血浆之间差异表达的 miRNAs。在 754 个 miRNAs 中，有 153 个相对于对照组有显著差异表达。在扩展的样本集中，包括浆液性、内胚层样和粘液性亚型，进一步验证了 7 个个体 miRNA（miR-200a、miR-200b、miR-200c、miR-141、miR-429、miR-1290 和 miR-30a-5p）的表达。所有 miR-200 家族成员和 miR-1290 明显过表达，而 miR-30a-5p 仅弱过表达。miRNA 表达区分病理样本与对照的能力很强。接收者操作特征曲线分析发现 miR-200a、miR-200c、miR-141、miR-429 和 miR-1290 的曲线下面积（AUC）值为 1.000，miR-200b 和 miR-30a-5p 的 AUC 值分别为 0.996 和 0.885。初步生存分析表明，miR-200b 的低表达水平与总生存时间较长显著相关（危险比[HR]：0.25，平均生存 44 个月），而高表达水平与总生存时间较短相关（HR：4.04，平均生存 24 个月）。我们的研究结果表明，腹水来源的 miRNAs 应进一步探索和评估，作为卵巢癌潜在的诊断和预后生物标志物。
