血浆 miRNA 作为卵巢癌诊断生物标志物的价值。

The Value of Plasma-Based MicroRNAs as Diagnostic Biomarkers for Ovarian Cancer.

机构信息

Intensive Care Unit, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Am J Med Sci. 2019 Oct;358(4):256-267. doi: 10.1016/j.amjms.2019.07.005. Epub 2019 Jul 17.

DOI:10.1016/j.amjms.2019.07.005

PMID:31353030

Abstract

BACKGROUND

Ovarian cancer (OC) is one of the most threatening diseases among women in the world. Plasma microRNAs (miRNAs) may serve as promising diagnostic biomarkers for patients with OC.

MATERIALS AND METHODS

Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based on Exiqon panel, we identified 27 differentially expressed miRNAs from 2 OC pool samples and 1 normal control (NC) pool in the initial screening phase. Then we further validated the identified miRNAs through the training (32 OC vs. 34 NCs) and validation stages (69 OC vs. 66 NCs) using qRT-PCR. The expression levels of the miRNAs were also assessed in tissues and exosomes.

RESULTS

Five plasma miRNAs (miR-205-5p, miR-145-5p, miR-10a-5p, miR-346 and miR-328-3p) were significantly overexpressed in OC in comparison with NCs. The areas under the receiver operating characteristic curve of the 5-miRNA panel were 0.788 for the training stage and 0.763 for the validation stage. The level of miR-205-5p has significantly different expression in patients with well-moderate histological grade compared with those with a poor grade (P = 0.012). The expression levels of the 5 miRNAs were also significantly upregulated in the exosomes of OC plasma samples (32 OC vs. 32 NCs). However, the expression of the 4 miRNAs (miR-145-5p, miR-10a-5p, miR-346 and miR-328-3p) was significantly lower in tumor samples than in normal tissues (22 OC vs. 22 NCs).

CONCLUSIONS

The 5 plasma miRNAs may be noninvasive diagnostic biomarkers of OC. The plasma miR-205-5p level may reflect the change trend of the histological grade of OC patients.

摘要

背景

卵巢癌（OC）是全球女性最具威胁性的疾病之一。血浆 microRNAs（miRNAs）可能成为 OC 患者有前途的诊断生物标志物。

材料与方法

在初始筛选阶段，我们使用基于 Exiqon 面板的定量逆转录聚合酶链反应（qRT-PCR），从 2 个 OC 池样本和 1 个正常对照（NC）池中共鉴定出 27 个差异表达的 miRNAs。然后，我们通过训练（32 个 OC 与 34 个 NC）和验证阶段（69 个 OC 与 66 个 NC）使用 qRT-PCR 进一步验证了鉴定出的 miRNAs。还评估了 miRNA 在组织和外泌体中的表达水平。

结果

与 NC 相比，OC 中 5 种血浆 miRNAs（miR-205-5p、miR-145-5p、miR-10a-5p、miR-346 和 miR-328-3p）表达显著上调。训练阶段 5- miRNA 组的曲线下面积为 0.788，验证阶段为 0.763。与组织学分级较差的患者相比，组织学分级较好的患者 miR-205-5p 水平的表达有显著差异（P=0.012）。OC 血浆样本外泌体中 5 种 miRNA 的表达水平也显著上调（32 个 OC 与 32 个 NC）。然而，与正常组织相比，肿瘤组织中 4 种 miRNA（miR-145-5p、miR-10a-5p、miR-346 和 miR-328-3p）的表达显著降低（22 个 OC 与 22 个 NC）。