High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer

High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer
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高通量蛋白质组学鉴定卵巢癌的高准确性11种血浆蛋白质生物标志物特征

DOI:
10.1038/s42003-019-0464-9
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发表时间:
2019-06-20
影响因子:
5.9
通讯作者:
Gyllensten, Ulf
Gyllensten, Ulf
中科院分区:
生物学2区
文献类型:
--
作者:
Enroth, Stefan;Berggrund, Malin;Gyllensten, Ulf

文献摘要

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卵巢癌通常在晚期被发现,总体5年生存率只有30%-40%。迫切需要更多的手段来进行早期发现和改进诊断。为了寻找新的生物标志物,我们使用邻近延伸分析(PEA)比较了卵巢癌和良性肿瘤患者三个队列中593个蛋白的循环血浆水平。开发了一种组合策略来识别不同的多变量生物标记物特征。由11个生物标记物加上年龄组成的最终模型被开发为以绝对浓度报告的多重PEA测试。最终的模型在第四个独立队列中进行了评估,对于卵巢癌I-IV期的检测,AUC=0.94,PPV=0.92,灵敏度=0.85,特异度=0.93。新的血浆蛋白标志物可用于提高附件卵巢肿块妇女的诊断,或用于筛查应参考专门检查的妇女。
Ovarian cancer is usually detected at a late stage and the overall 5-year survival is only 30-40%. Additional means for early detection and improved diagnosis are acutely needed. To search for novel biomarkers, we compared circulating plasma levels of 593 proteins in three cohorts of patients with ovarian cancer and benign tumors, using the proximity extension assay (PEA). A combinatorial strategy was developed for identification of different multivariate biomarker signatures. A final model consisting of 11 biomarkers plus age was developed into a multiplex PEA test reporting in absolute concentrations. The final model was evaluated in a fourth independent cohort and has an AUC = 0.94, PPV = 0.92, sensitivity = 0.85 and specificity = 0.93 for detection of ovarian cancer stages I-IV. The novel plasma protein signature could be used to improve the diagnosis of women with adnexal ovarian mass or in screening to identify women that should be referred to specialized examination.