A combination of circulating miRNAs for the early detection of ovarian cancer.

A combination of circulating miRNAs for the early detection of ovarian cancer.
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DOI:
10.18632/oncotarget.20688
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发表时间:
2017-10-27
期刊:
影响因子:
--
通讯作者:
Ochiya T
Ochiya T
中科院分区:
其他
文献类型:
--
作者:
Yokoi A;Yoshioka Y;Hirakawa A;Yamamoto Y;Ishikawa M;Ikeda SI;Kato T;Niimi K;Kajiyama H;Kikkawa F;Ochiya T

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由于早期发现困难,卵巢癌是导致妇科癌症死亡的主要原因。目前的筛查方法缺乏足够的准确性,提出一种新的早期检测方法,以更小的侵入性改善患者的预后仍然具有挑战性。尽管许多研究表明循环microrna在癌症检测中的效用,但它们在早期检测中的潜力仍然难以捉摸。在这里,我们利用8种循环血清mirna的组合开发了新的预测模型。该方法能够成功区分卵巢癌患者与健康对照(曲线下面积0.97,灵敏度0.92,特异性0.91),早期卵巢癌与良性肿瘤患者(分别为0.91,0.86和0.83)。该方法还可以对4种类型的上皮性卵巢癌进行亚型分类。此外,研究发现,这8种mirna中的大多数被包装在细胞外囊泡(包括来自卵巢癌细胞的外泌体)中,并在小鼠血液中循环。本研究描述的循环mirna可能作为卵巢癌患者的生物标志物。手术前的早期检测和亚型确定对于临床医生为每位患者设计有效的治疗策略至关重要,这也是精准医学的目标。
Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs. This method was able to successfully distinguish ovarian cancer patients from healthy controls (area under the curve, 0.97; sensitivity, 0.92; and specificity, 0.91) and early-stage ovarian cancer from patients with benign tumors (0.91, 0.86 and 0.83, respectively). This method also enables subtype classification in 4 types of epithelial ovarian cancer. Furthermore, it is found that most of the 8 miRNAs were packaged in extracellular vesicles, including exosomes, derived from ovarian cancer cells, and they were circulating in murine blood stream. The circulating miRNAs described in this study may serve as biomarkers for ovarian cancer patients. Early detection and subtype determination prior to surgery are crucial for clinicians to design an effective treatment strategy for each patient, as is the goal of precision medicine.