CA125, YKL-40, HE-4 and Mesothelin: a new serum biomarker combination in discrimination of benign and malign epithelial ovarian tumor

Objective: Cancer Antigen 125 (CA125) and Risk of Ovarian Malignancy Algorithm (ROMA) score are used for classification of ovarian masses (benign/malign) in preoperative stage. However, their discrimination capacity are considered insufficient, and greatly effected by histological subtype and menopausal status. This study aimed to investigate diagnostic performance of Human epididymis protein 4 (HE4), Y (tyrosine), K (lysine), and L (leucine)-40 (YKL-40), Mesothelin, Rho GDP dissociation inhibitor beta (LyGDI), CA125 or their combinations in discrimination of benign/malign ovarian diseases in preoperative stage. Materials and methods: The study groups were comprised sera of 31 epithelial ovarian cancer (EOC), 30 benign ovarian tumor patients, and 32 healthy women. The diagnostic performance of the biomarkers were evaluated based on ROC-AUC values and logistic regression analysis incorporating menopausal status and clinical diagnosis of the subjects. Results: Our data demonstrates that "CA125-HE4-Mesothelin-YKL-40" had the highest sensitivity at 80%, 90%, 95% specificity 96.8%, 93.6%, 93.6%, respectively. Conclusion: This study provides the first evidence for the combinational uses of "CA125-HE4-Mesothelin-YKL-40" as a panel in distinguishing malign from benign ovarian tumor, not affected by menopausal status unlike ROMA. However, higher patient number may also provide the evaluation of this panel in malign group in terms of tumor stages.