1Department of Immunology, Genetics, and Pathology, Biomedical Center, Science for Life Laboratory (SciLifeLab) Uppsala, Box 815, Uppsala University, SE-75108 Uppsala, Sweden.
2Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
Commun Biol. 2019 Jun 20;2:221. doi: 10.1038/s42003-019-0464-9. eCollection 2019.
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.
卵巢癌通常在晚期才被发现，整体 5 年生存率仅为 30-40%。因此迫切需要额外的早期检测和改进的诊断手段。为了寻找新的生物标志物，我们使用邻近延伸分析（PEA）比较了三组卵巢癌和良性肿瘤患者的循环血浆中 593 种蛋白质的水平。开发了一种组合策略来识别不同的多变量生物标志物特征。最终的模型由 11 个生物标志物加上年龄组成，并转化为一种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，对于检测卵巢癌 I-IV 期，AUC=0.94，PPV=0.92，敏感性=0.85，特异性=0.93。该新型血浆蛋白标志物可用于提高附件卵巢肿块妇女的诊断水平，或用于筛查以确定应转介至专科检查的妇女。
