Increased sialylation and reduced fucosylation of exfoliated cervical cells are potential markers of carcinogenesis in the cervix.

Abstract

The Pap test has been used for over 50 years for primary screening of cervical cancer. There has been no study of glycosylation changes in Pap test samples despite considerable potential of the glycosylation changes as biomarkers for detecting cancerous lesions. In this study, we developed a 96-well platform for enzyme-linked lectin assays (ELLAs) to evaluate glycosylation levels in cervical cells. A total of 117 samples of exfoliated cervical cells (ECCs) from 37 individuals with normal cytology, 20 with cervical intraepithelial neoplasia (CIN) 1, 19 with CIN 2, 26 with CIN 3 and 15 with cervical cancer were analyzed by ELLAs. The wells of 96-well plates were coated with lysates of the cervical cells, and sialylation and fucosylation levels were compared between the groups. Sialylation levels increased and fucosylation levels decreased with increasing grade of cervical dysplasia. ELLAs for sialylation [ELLA-Sambucus nigra (SNAs)] and fucosylation [ELLA-Aleuria aurantia lectin (AAL)] discriminated not only CIN 2 and worse (CIN 2+: CIN 2, CIN 3, and cancer) from normal cytology but also CIN 3 and worse (CIN 3+: CIN3 and cancer) from normal cytology. ELLA-SNAs and ELLA-AALs distinguished cancer from normal cytology with a high true-positive rate (TPR) (ELLA-SNAs: 87%; ELLA-AALs: 87%) and low false-positive rate (FPR) (ELLA-SNAs: 19%; ELLA-AALs: 11%). The sialylation and fucosylation levels of ECCs as measured by ELLAs have great potential as biomarkers for primary screening of cervical cancer.