Glycan Biomarkers for Cholangiocarcinoma

Cholangiocarcinoma (CCA) is an epithelial cancer arising in the biliary mucosa lining the ducts that carry bile from the liver to the small intestine. CCA is the second most common type of liver cancer after hepatocellular carcinoma (HCC) and is a highly lethal cancer. CCA is classified based on the anatomic location into intrahepatic CCA (iCCA), perihilar CCA (pCCA), or distal (dCCA) subtypes. The limited clinical presentation of these tumors contributes to late diagnosis with surgery being possible in less than 25% of patients and this, combined with high tumor recurrence after surgery, results in dismal prognosis and high mortality rates. Indeed, and in contrast to many other cancers, the overall mortality of CCA has not significantly improved, resulting in unsatisfactory 5-year survival rates (7–20%). The serum tumor marker carbohydrate antigen (CA) 19-9 is used in routine practice to help CCA diagnosis and to monitor disease progression once diagnosis has been achieved. The major limitation is the low sensitivity and specificity of this marker, thus not allowing the early detection of CCA. We have recently identified changes in glycosylation that occur in both tissue and serum of those with CCA. Importantly, these glycan changes could be used to differentiate CCA tissue or serum from healthy or diseased serum or tissue, including hepatocellular carcinoma and PSC. We hypothesize that these changes in glycosylation observed directly in CCA tissue, and in serum, may be useful as a non- invasive liquid biopsy biomarker of CCA. Thus, in this application we propose to develop new and novel biomarkers of CCA based upon the glycan changes observed in tissue and serum.