Schröder Lars, Rupp Alexander B A, Gihr Kathrin M E, Kobilay Makbule, Domroese Christian M, Mallmann Michael R, Holdenrieder Stefan
Department of Obstetrics and Gynecology, University Hospital Cologne, 50931 Cologne, Germany.
Department of Obstetrics and Gynecology, Ketteler Hospital, 63071 Offenbach, Germany.
Cancers (Basel). 2023 Oct 20;15(20):5081. doi: 10.3390/cancers15205081.
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.
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.
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.
HMGB1 and sRAGE have differential diagnostic potential for ovarian cancer detection and warrant inclusion in further validation studies.
高迁移率族蛋白B1（HMGB1）、晚期糖基化终产物可溶性受体（sRAGE）以及程序性细胞死亡标志物PD-1和PD-L1是具有免疫原性的血清生物标志物，可能作为癌症诊断的新型诊断工具。
我们使用酶免疫分析法对231名女性的血清中的这四种标志物进行了研究，其中76名患有卵巢癌，87名患有良性疾病，68名是健康对照者。使用受试者工作特征（ROC）曲线计算组间差异以及固定特异性为90%和95%时的敏感性。
与良性疾病患者和健康对照者相比，癌症患者的HMGB1水平显著升高，sRAGE水平降低。因此，HMGB1与sRAGE的比值在各诊断组之间的区分效果最佳。用于区分癌症与健康组的ROC曲线下面积（AUC），HMGB1为0.77，sRAGE为0.65，HMGB1/sRAGE比值为0.78；用于区分癌症与良性疾病组时略低，HMGB1为0.72，sRAGE为0.61，两者比值为0.74。在特异性为90%时检测癌症与良性疾病相比，HMGB1的敏感性最高，为41.3%，HMGB1/sRAGE比值为39.2%，其次是sRAGE，为18.9%。PD-1在区分卵巢癌和良性疾病方面仅显示出微小差异，而PD-L1则无区分能力。
HMGB1和sRAGE在卵巢癌检测中具有不同的诊断潜力，值得纳入进一步的验证研究。
