Development of a novel cancer diagnostic method targeting glycosylation on specific molecules

抄録

WFDC2, also known as HE4, is a member of whey acidic protein four-disulfide core, which was first identified in human epididymis. It is strongly expressed in ovarian cancer whereas its expression is substantially low in benign tissues; WFDC2 is, therefore, currently clinically approved as a biomarker for ovarian cancer. Although little is known about its function, WFDC2 has been reported to exist as a glycosylated form when secreted. Here, we show that there exist certain lectins that specifically react with glycosylation on secreted WFDC2 and they are detectable by lectin ELISA using those lectins. First, we established WFDC2-expressing cell and confirmed the glycosylation of secreted WFDC2. After the synthesis of WFDC2, it was applied to lectin array. The result indicated that there exist several lectins that specifically react with glycosylation on WFDC2. With an anti-WFDC2 antibody and lectins that recognize the specific glycans, we established lectin ELISA and examined plasma samples from patients of several kinds of cancers and healthy donors. It was revealed that WFDC2 from gastric and colorectal cancer patients exhibited apparently stronger reaction to lectins than healthy donors. Taken together, glycans on WFDC2 are regarded as potential biomarkers that increase specificity and sensitivity for detecting various kinds of cancer.