Exosomal let-7d-3p and miR-30d-5p as diagnostic biomarkers for non-invasive screening of cervical cancer and its precursors
Exosomal let-7d-3p and miR-30d-5p as diagnostic biomarkers for non-invasive screening of cervical cancer and its precursors
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外泌体let-7d-3p和miR-30d-5p作为宫颈癌及其癌前病变无创筛查的诊断生物标志物
DOI：
10.1186/s12943-019-0999-x
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发表时间：
2019-04-02
期刊：
影响因子：
37.3
通讯作者：
Lu, Yan
中科院分区：
文献类型：
--
作者：
Zheng, Mengyue;Hou, Ling;Lu, Yan
通过检测和治疗高度宫颈上皮内瘤变（CIN）进行宫颈癌筛查是预防癌症最成功的方法。然而，目前宫颈癌筛查测试的准确性仍然很低。本研究的目的是开发一种基于循环外泌体miRNA的更准确的方法。进行miRNA测序以在来自健康志愿者、宫颈癌患者和CIN患者的121个血浆样品中鉴定作为诊断生物标志物的候选外泌体miRNA。鉴定了一组具有8种差异表达的外泌体miRNAs，以区分CIN II+组（包括晚期CIN II患者）和CIN I−组（包括CIN I患者和健康志愿者）中的患者。Let-7 d-3 p和miR-30 d-5 p在宫颈肿瘤和癌旁正常组织中差异有统计学意义（P < 0.005），在血浆样本中表现出一致的趋势，并在203份独立血浆样本中得到进一步验证。整合这两种miRNA得到的AUC值为0.828，以区分CIN II+组和CIN I−组的患者。将它们进一步整合到基于细胞学检测的模型中，导致AUC更高，为0.887，而仅基于细胞学检测的AUC值为0.766。总之，血浆外泌体miR-30 d-5 p和let-7 d-3 p是用于宫颈癌及其前体的非侵入性筛查的有价值的诊断生物标志物。临床诊断需要使用大样本量进行进一步验证。
Cervical cancer screening through detection and treatment of high-grade cervical intraepithelial neoplasia (CIN) is most successful in cancer prevention. However, the accuracy of the current cervical cancer screening tests is still low. The aim of this study was to develop a more accurate method based on circulating exosomal miRNAs. The miRNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 121 plasma samples from healthy volunteers, cervical carcinoma patients, and CIN patients. A panel with eight differentially expressed exosomal miRNAs was identified to distinguish patients in the CIN II+ group (including advanced CIN II patients) from those in the CIN I− group (including CIN I patients and healthy volunteers). Let-7d-3p and miR-30d-5p showed significant difference between cervical tumors and adjacent normal tissues (P < 0.005), exhibited a consistent trend in plasma samples, and were further validated in 203 independent plasma samples. Integrating these two miRNAs yielded an AUC value of 0.828 to distinguish patients in CIN II+ group from those in CIN I− group. Further integrating them into a cytological test-based model resulted in a higher AUC of 0.887, while the AUC value based on the cytological test alone was 0.766. In summary, plasma exosomal miR-30d-5p and let-7d-3p are valuable diagnostic biomarkers for non-invasive screening of cervical cancer and its precursors. Further validation using large sample sizes is required for clinical diagnosis.