Novel Glycobiomarker for Ovarian
Cancer That Detects
Clear Cell Carcinoma
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Abstract
Epithelial
ovarian cancer (EOC) is often asymptomatic and thus
diagnosed at advanced stages with a poor prognosis. False-negative
results for the conventional marker CA125 frequently occur in cases
of clear cell carcinoma (CCC), a type of EOC; therefore, it is necessary
to develop biomarkers with greater sensitivity. We previously reported
a strategy to discover glycobiomarker candidates by combined lectin
microarray and IGOT–LC/MS analysis. We have now optimized this
strategy for discovering EOC biomarkers. Glycopeptides possessing
cancerous glycans were enriched from the ascites fluids and culture
supernatants of cancer cell lines with a fucose-binding lectin, AAL.
IGOT–LC/MS analysis of CCC samples yielded 144 candidate glycoproteins.
We selected WFA by lectin microarray as the optimal lectin to distinguish
EOC from gastric and colon cancer. The candidates were narrowed by
Western
analysis of the WFA-bound fraction of ascites fluids. One of the final
candidates, WFA-reactive ceruloplasmin, produced higher signals in
the ascites fluids of EOC patients, including CCC, in comparison with
the benign samples, while CA125 levels were comparable in the sandwich
ELISA. Thus, our glycoproteomic strategy featuring efficient enrichment
of glycans with disease-related alterations is applicable to various
diseases