评估蛋白生物标志物在术前鉴别卵巢良恶性肿瘤中的作用。

Assessment of protein biomarkers for preoperative differential diagnosis between benign and malignant ovarian tumors.

机构信息

Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy; Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, KU Leuven, Leuven, Belgium; Department of Development and Regeneration, KU Leuven, Leuven, Belgium; Queen Charlotte's and Chelsea Hospital, Imperial College, London, UK.

Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, KU Leuven, Leuven, Belgium.

出版信息

Gynecol Oncol. 2020 Dec;159(3):811-819. doi: 10.1016/j.ygyno.2020.09.025. Epub 2020 Sep 29.

DOI:10.1016/j.ygyno.2020.09.025

PMID:32994054

Abstract

OBJECTIVE

To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors.

METHODS

In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs.

RESULTS

CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80.

CONCLUSIONS

The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

摘要

目的

评估肿瘤和免疫相关蛋白在鉴别良恶性附件肿块，以及不同肿瘤亚组中的诊断价值。

方法

在这项探索性诊断研究中，连续纳入了 254 名计划手术的附件肿块患者（128 例良性、42 例交界性、22 例 I 期、55 例 II-IV 期和 7 例继发性转移性肿瘤）。使用多重高通量免疫分析（Luminex）和电化学发光免疫分析（ECLIA）术前检测了 33 种血清蛋白的定量。计算了单变量受试者工作特征曲线（ROC）下的面积（AUC）。为了区分恶性和良性肿瘤，使用带向后消除的脊线逻辑回归进行了多变量分析，并使用自举法验证了得到的 AUC。

结果

CA125 区分良恶性肿瘤的单变量 AUC 最高（0.85，95%置信区间 0.79-0.89）。将 CA125 与 CA72.4 和 HE4 结合使用可将 AUC 提高至 0.87。对于良性与交界性肿瘤，CA125 的单变量 AUC 最高（0.74）。对于交界性与 I 期恶性肿瘤，没有蛋白有前景。对于 I 期与 II-IV 期恶性肿瘤，CA125、HE4、CA72.4、CA15.3 和 LAP 的单变量 AUC 均≥0.80。