Clinical usefulness of E4-phytohemagglutinin reactive C4-binding protein relative front value in serum for distinguishing between ovarian clear cell adenocarcinoma and endometrioma

Abstract

Background and aims

We identified a fully sialylated glycopeptide of the α-chain of Complement 4 binding protein (C4BP) in blood using Liquid chromatography/Mass spectrometry, which helps differentiate ovarian clear cell carcinoma (OCCC) from endometrioma (EM). We aimed to develop a blood measurement system to immunologically assess fully sialylated α-chain of C4BP, specifically E4-phytohemagglutinin-reactive C4BP (P-C4BP-Rf).

Materials and methods

Ninety-seven serum samples were collected from healthy (HE) (n = 11), uterine fibroid (UF) patients (n = 15), EM patients (n = 32), and OCCC patients (n = 39). P-C4BP-Rf was measured using lectin affinity electrophoresis and antibody affinity blotting. CA125 and human epididymal protein 4 (HE4) levels were also measured and compared. We selected 22 EM and 24 OCCC with no significant differences in CA125 levels. Tissue factor pathway inhibitor 2 (TFPI2) and FS-C4BP were added to the analysis to distinguish OCCC from EM using five biomarkers.

Results

P-C4BP-Rf was significantly higher in OCCC than in HE, UF, and EM (P < 0.0001). AUC values were: CA125, 0.547; HE4, 0.850; TFPI2, 0.847; FS-C4BP, 0.715; and P-C4BP-Rf, 0.887. The combination of P-C4BP-Rf and HE4 yielded the highest AUC (0.960).

Conclusion

P-C4BP-Rf is useful for distinguishing OCCC from EM and may be more accurate when combined with HE4.