国际妇产科学杂志

国际妇产科学杂志 ›› 2020, Vol. 47 ›› Issue (4): 462-468.

• 论著 • 上一篇    下一篇

外泌体生物标志物在卵巢癌诊断及预后评估方面的价值——系统评价

李耀威，李力   

  1. 530021  南宁，广西医科大学附属肿瘤医院妇科暨区域性高发肿瘤早期防治研究教育部重点室验室[李耀威（现工作单位为上虞人民医院妇产科），李力]
  • 收稿日期:2020-04-30 修回日期:2020-05-18 出版日期:2020-08-15 发布日期:2020-08-15
  • 通讯作者: 李力，E-mail：lili@gxmu.edu.cn E-mail:lili@gxmu.edu.cn
  • 基金资助:
    广西科技计划项目（桂科攻14124004）；广西自然科学基金项目（2014GXNSFAA118147）

The Value of Exosome Biomarkers in the Diagnosis and Prognostic Evaluation of Ovarian Cancer--Systematic Review

LI Yao-wei，LI Li   

  1. Department of Gynecology & Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor of Ministry of Education，Affiliated Tumor Hospital of Guangxi Medical University，Nanning 530021，China [LI Yao-wei（The Current Working Unit is Department of Obstetrics and Gynecology，Shangyu People′s Hospital），LI Li]
  • Received:2020-04-30 Revised:2020-05-18 Published:2020-08-15 Online:2020-08-15
  • Contact: LI Li，E-mail：lili@gxmu.edu.cn E-mail:lili@gxmu.edu.cn

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摘要： 目的：系统评价外泌体生物标志物在卵巢癌诊断和预后评估方面的价值。方法：计算机检索中国知网、维普、万方、PubMed、EMBASE、Web of Knowledge 和Cochrane Library数据库，搜集外泌体在卵巢癌诊断和预后方面的相关研究，检索时间均从建库至2019年12月20日。由2名研究者按照纳入与排除标准筛选文献、提取资料和评价纳入研究的质量。在诊断方面，比较卵巢癌患者和非卵巢癌对照人群外泌体生物标志物的表达情况。在预后方面，评价外泌体生物标志物表达与卵巢癌患者总生存期（OS）、无进展生存期（PFS）之间的相关性。结果：共纳入文献10篇。利用外泌体提取试剂盒是分离纯化外泌体的最常见方法，透射电子显微镜观察形态和检测外泌体标志蛋白是鉴定外泌体的基本方法。①诊断方面，血清来源外泌体内含miR-200a、miR-145显示出较高的诊断价值（miR-200a的AUC为0.91，敏感度和特异度分别为83.9%和90.0%；miR-145的AUC为0.91，敏感度和特异度分别为91.7%和75.0%）。血浆来源外泌体内含纤维蛋白原α链（FGA）、凝溶胶蛋白（GSN）、纤维蛋白原γ链（FGG）也具有一定的诊断价值（FGA、GSN、FGG的AUC分别为0.85、0.83和0.74）。②预后评估方面，血清来源外泌体内含miR-373、miR-200b、miR-200c高表达与卵巢癌患者的OS明显缩短密切相关（HR分别为2.1、2.7和2.4，95%CI分别为1.0～4.3、1.3～5.7和1.2～4.9）；miR-200c的高表达与卵巢癌患者PFS缩短也密切相关（HR=2.0，95%CI：1.1～3.6）。血清来源外泌体内含长链非编码RNA反义缺氧诱导因子（lncRNA aHIF）的高表达与卵巢癌患者OS缩短密切相关（HR=3.70，95%CI：1.83～7.50）。结论：外泌体生物标志物可用于卵巢癌患者的早期诊断和预后评估。

关键词: 卵巢肿瘤；, 外泌体；, 生物标记；, 诊断；, 预后

Abstract: Objective: To systematically evaluate the value of exosome biomarkers in the diagnosis and prognosis of ovarian cancer (OC). Methods: The databases of CNKI, VIP, WanFang, PubMed, EMBASE, Web of Knowledge and Cochrane Library were searched to collect relevant researches on the diagnosis and prognosis of OC with exosome biomarkers by computers. Dated from the establishments of the databases to 20th December, 2019. Two reviewers screened research papers according to the inclusion and exclusion criteria, extracted data and assessed the risk bias of included studies. For diagnostic evaluation, the differences in the expression of exosome biomarkers between OC patients and non-OC controls were analyzed. For prognosis prediction, the correlation between the expression levels of exosome biomarkers and overall survival (OS) and disease free survival (DFS) of OC was analyzed. Results: A total of 10 studies were included. The exosomes extraction kit method was the most common method for purifying exosomes. Transmission electron microscope observation of morphology and detection of exosomal marker proteins were the basic methods for identifying exosomes. For diagnostic evaluation, serum-derived exosomes containing miR-200a, miR-145 showed high diagnostic value (the AUC of miR-200a was 0.91, sensitivity and specificity of which reached 83.9% and 90.0%, respectively; the AUC of miR-145 was 0.91, sensitivity and specificity of which reached 91.7% and 75.0%, respectively). Plasma-derived exosomes containing proteins fibrinogen alpha chain (FGA), gelsolin (GSN), and fibrinogen gamma chain (FGG) also had certain diagnostic values (the AUC of FGA, GSN, and FGG can reach 0.85, 0.83 and 0.74, respectively). For prognosis prediction, the high expression of miR-373, miR-200b and miR-200c from serum-derived exosomes was closely related to poorer OS in OC patients (HR was 2.1, 2.7, and 2.4; 95%CI were 1.0-4.3, 1.3-5.7 and 1.2-4.9); Similarly, the high expression of miR-200c in OC patients was also closely related to poorer PFS (HR=2.0, 95%CI: 1.1-3.6). Serum-derived exosomes containing long non-coding RNA aHIF was closely related to poorer OS in patients with OC (HR=3.70, 95%CI: 1.83-7.50). Conclusions: Exosome biomarkers could be used for early diagnosis and prognostic evaluation of patient with OC.

Key words: Ovarian neoplasms；, Exosomes；, Biomarkers；, Diagnosis；, Prognosis