上皮性卵巢癌（EOC）通常在晚期被诊断，并且具有较高的死亡率。在本研究中，我们使用Olink Proteomics的接近扩展物法（proximity extension assay）寻找新的血浆蛋白生物标志物，以预测EOC患者的整体生存率（OS）。从116名接受原发性去肿术的EOC患者，其中包括28例早期EOC（FIGO分期I-II）和88例晚期EOC（FIGO分期III-IV），术前采集外周血样本。使用Olink Oncology II和Inflammation面板测量蛋白质。总共分析了177个独特的蛋白质生物标志物。将交叉验证和LASSO回归相结合以选择OS的预测模型。包括年龄和三种生物标志物组合神经营养素3（NT-3）+跨膜糖蛋白NMB（GPNMB）+中皮素（MSLN）的模型预测了较差的OS，AUC = 0.79（p = 0.004）。将癌抗原125（CA125）和人类附睾蛋白4（HE4）添加到模型中进一步提高了性能（AUC = 0.83；p = 0.003）。在包括年龄和分期（III + IV vs.I + II）的术后模型中，趋化因子（C-C基序）配体28（CCL28）+ T细胞白血病/淋巴瘤蛋白1A（TCL1A）+ GPNMB的三种生物标志物组合改善了OS的预测（从AUC = 0.83提高到AUC = 0.90；p = 0.05）。在包括年龄和分为两组的分期（III vs. I + II）的术后模型中，生物标志物CCL28和GPNMB1改善了OS的预测（AUC = 0.86；p <0.001）。同时具有高水平的CA125和HE4可预测更差的生存率（p = 0.05）。在评估血浆蛋白质生物标志物预测OS表现的探索性研究中，我们发现添加生物标志物（特别是NT-3）到组合中改善了OS的预测。 版权所有©2023年，国际抗癌研究所（George J. Delinasios医生），保留所有权利。

Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC.Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS.The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p<0.001). The combination of high levels of both CA125 and HE4 predicted worse survival (p=0.05).In this explorative study evaluating the performance of plasma protein biomarkers in predicting OS, we found that adding biomarkers, especially NT-3, to the panel improved the prediction of OS.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.