血清叶酸受体α、间皮素和巨核细胞促进因子在卵巢癌中的表达：与疾病分期和分级的关系，并与 CA125 和 HE4 的比较。

BACKGROUND: Evaluate and compare the utility of serum folate receptor alpha (FRA) and megakaryocyte potentiating factor (MPF) determinations relative to serum CA125, mesothelin (MSLN) and HE4 for the diagnosis of epithelial ovarian cancer (EOC). METHODS: Electrochemiluminescent assays were developed for FRA, MSLN and MPF and used to assess the levels of these biomarkers in 258 serum samples from ovarian cancer patients. Commercial assays for CA125 and HE4 were run on a subset of 176 of these samples representing the serous histology. Data was analyzed by histotype, stage and grade of disease. A comparison of the levels of the FRA, MSLN and MPF biomarkers in serum, plasma and urine was also performed in a subset of 57 patients. RESULTS: Serum and plasma levels of FRA, MSLN and MPF were shown to be highly correlated between the two matrices. Correlations between all pairs of markers in 318 serum samples were calculated and demonstrated the highest correlation between HE4 and MPF, and the lowest between FRA and MPF. Serum levels of all markers showed a dependence on both stage and grade of disease. A multi-marker logistic regression model was developed resulting in an AUC=0.91 for diagnosis of serous ovarian cancer, a significant improvement over the AUC for any of the individual markers, including CA125 (AUC=0.84). CONCLUSIONS: FRA has significant potential as a biomarker for ovarian cancer, both as a stand-alone marker and in combination with other known markers for EOC. The lack of correlation between the various markers analyzed in the present study suggests that a panel of markers can aid in the detection and/or monitoring of this disease.

背景：评估和比较血清叶酸受体α（FRA）和巨核细胞增强因子（MPF）与血清 CA125、间皮素（MSLN）和 HE4 测定在诊断上皮性卵巢癌（EOC）方面的效用。

方法：开发了电化学发光测定法用于 FRA、MSLN 和 MPF，并用于评估 258 份卵巢癌患者血清样本中这些生物标志物的水平。对其中 176 份代表浆液性组织学的样本进行了 CA125 和 HE4 的商业测定。通过疾病的组织类型、分期和分级对数据进行了分析。还在 57 名患者的亚组中比较了血清、血浆和尿液中 FRA、MSLN 和 MPF 生物标志物的水平。

结果：血清和血浆中的 FRA、MSLN 和 MPF 水平在两种基质之间显示出高度相关性。在 318 份血清样本中计算了所有标志物对之间的相关性，并显示 HE4 与 MPF 之间相关性最高，而 FRA 与 MPF 之间相关性最低。所有标志物的血清水平均依赖于疾病的分期和分级。建立了多标志物逻辑回归模型，用于诊断浆液性卵巢癌的 AUC=0.91，明显优于任何单个标志物（包括 CA125，AUC=0.84）的 AUC。

结论：FRA 作为卵巢癌的生物标志物具有重要的潜力，无论是作为独立标志物还是与其他已知的 EOC 标志物联合使用。本研究中分析的各种标志物之间缺乏相关性表明，一组标志物可以辅助检测和/或监测这种疾病。