Background: High mobility group box 1 (HMGB1), soluble receptor of advanced glycation end products (sRAGE) and programmed cell death markers PD-1 and PD-L1 are immunogenic serum biomarkers that may serve as novel diagnostic tools for cancer diagnosis. Methods: We investigated the four markers in sera of 231 women, among them 76 with ovarian cancer, 87 with benign diseases and 68 healthy controls, using enzyme immunoassays. Discrimination between groups was calculated using receiver operating characteristic (ROC) curves and sensitivities at fixed 90% and 95% specificities. Results: HMGB1 levels were significantly elevated and sRAGE levels were decreased in cancer patients as compared to benign and healthy controls. In consequence, the ratio of HMGB1 and sRAGE discriminated best between diagnostic groups. The areas under the curve (AUCs) of the ROC curves for differentiation of cancer vs. healthy were 0.77 for HMGB1, 0.65 for sRAGE and 0.78 for the HMGB1/sRAGE ratio, and slightly lower for the differentiation of cancer vs. benigns with 0.72 for HMGB1, 0.61 for sRAGE and 0.74 for the ratio of both. The highest sensitivities for cancer detection at 90% specificity versus benign diseases were achieved using HMGB1 with 41.3% and the HMGB1/sRAGE ratio with 39.2%, followed by sRAGE with 18.9%. PD-1 showed only minor and PD-L1 no power for discrimination between ovarian cancer and benign diseases. Conclusion: HMGB1 and sRAGE have differential diagnostic potential for ovarian cancer detection and warrant inclusion in further validation studies.
背景：高迁移率族蛋白B1（HMGB1）、可溶性晚期糖基化终末产物受体（sRAGE）以及程序性细胞死亡标志物PD-1与PD-L1是具有免疫原性的血清生物标志物，可能成为癌症诊断的新型检测工具。方法：我们采用酶免疫分析法检测了231名女性血清中的四种标志物，其中包括76例卵巢癌患者、87例良性病变患者及68例健康对照者。通过受试者工作特征（ROC）曲线及固定90%与95%特异性下的灵敏度评估各组间的鉴别能力。结果：与良性病变组及健康对照组相比，癌症患者的HMGB1水平显著升高而sRAGE水平降低。因此，HMGB1与sRAGE的比值在诊断组间展现出最佳鉴别效能。在区分癌症与健康对照的ROC曲线中，HMGB1的曲线下面积（AUC）为0.77，sRAGE为0.65，HMGB1/sRAGE比值为0.78；而在区分癌症与良性病变时，HMGB1的AUC为0.72，sRAGE为0.61，两者比值为0.74。在针对良性病变设定90%特异性的条件下，HMGB1对癌症检测的灵敏度最高（41.3%），HMGB1/sRAGE比值次之（39.2%），sRAGE为18.9%。PD-1对卵巢癌与良性病变的鉴别能力较弱，PD-L1则无显著鉴别价值。结论：HMGB1与sRAGE在卵巢癌检测中具有差异诊断潜力，值得纳入后续验证研究。
Immunogenic Biomarkers HMGB1 and sRAGE Are Potential Diagnostic Tools for Ovarian Malignancies
肿瘤(癌症)患者之家