Immunogenic Biomarkers HMGB1 and sRAGE Are Potential Diagnostic Tools for Ovarian Malignancies

Abstract

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.