Diagnosis of epithelial ovarian cancer using a combined protein biomarker panel

Diagnosis of epithelial ovarian cancer using a combined protein biomarker panel
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DOI:
10.1038/s41416-019-0544-0
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发表时间:
2019-09-10
影响因子:
8.8
通讯作者:
Graham, Robert L. J.
Graham, Robert L. J.
中科院分区:
医学1区
文献类型:
--
作者:
Russell, Matthew R.;Graham, Ciaren;Graham, Robert L. J.

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背景技术背景:EOC的早期检测工具构建从生物标志物的表达数据从血清收集UKCTOCS.METHODS分析:本研究包括49 EOC病例(19 I型和30 II型)和31个对照组,代表482系列样本跨越7年前诊断。通过分析四种推定的生物标志物的表达数据的失调来训练logit模型,(CA 125,磷脂酰胆碱-固醇酰基转移酶,维生素K依赖性蛋白Z和C-反应蛋白);通过对每个个体与基线表达失调相关的特异性进行评分。该模型是歧视性的,通过k倍和留一交叉验证,并在I型EOC集进一步验证。样本作为模拟年度筛查程序进行分析,算法诊断出诊断前1-2年PPV>30%的病例。对于II型病例(类似于80%的HGS)的算法分类64%,在1年和28%,在2年tDx为severe.CONCLUSIONS:该面板有可能诊断EOC一,二年前比目前的诊断。这种分析提供了一个具体的工作实例,展示了开发作为筛选工具和审查其属性的潜力。限制所施加的样品数量的解释进行了讨论。
BACKGROUND: An early detection tool for EOC was constructed from analysis of biomarker expression data from serum collected during the UKCTOCS.METHODS: This study included 49 EOC cases (19 Type I and 30 Type II) and 31 controls, representing 482 serial samples spanning seven years pre-diagnosis. A logit model was trained by analysis of dysregulation of expression data of four putative biomarkers, (CA125, phosphatidylcholine-sterol acyltransferase, vitamin K-dependent protein Z and C-reactive protein); by scoring the specificity associated with dysregulation from the baseline expression for each individual.RESULTS: The model is discriminatory, passes k-fold and leave-one-out cross-validations and was further validated in a Type I EOC set. Samples were analysed as a simulated annual screening programme, the algorithm diagnosed cases with >30% PPV 1-2 years pre-diagnosis. For Type II cases (similar to 80% were HGS) the algorithm classified 64% at 1 year and 28% at 2 years tDx as severe.CONCLUSIONS: The panel has the potential to diagnose EOC one-two years earlier than current diagnosis. This analysis provides a tangible worked example demonstrating the potential for development as a screening tool and scrutiny of its properties. Limits on interpretation imposed by the number of samples available are discussed.