Association between the expression of core 3 synthase and survival outcomes of patients with cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is a highly aggressive and metastatic type of malignant carcinoma that is associ- ated with high mortality rates and is difficult to detect at early stages. Core 3 structure is a mucin-type O-glycans synthesized by β1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase), which plays an important role in the diges- tive system, in particular gastrointestinal goblet cells. It has been reported that core 3 synthase-expressing cells show lower migratory and invasive rates, and lower metastatic activity. A immunohistochemical study also showed that this enzyme was expressed in normal epithelial cells of the colon, but completely disappeared in colorectal cancer cells. The present study aimed to identify biomarkers that could be used to predict the prognosis of patients with CCA. Pathological specimens of 185 CCA tissues were immunohistochemically stained with two antibodies, G8-144 and MECA-79, which recognize core 3 synthase and 6-sulfated N-acetyllactosamine on the extended core-1 O-glycans, respectively. The asso- ciation between G8-144 or MECA-79 positivity and patient prognosis was statistically analyzed. Positive expression of G8-144 was associated with improved prognosis in patients with distal CCA (dCCA). Patients with dCCA positive for G8-144 showed lower mortality rates than those with negative expression. However, the positive expression of MECA-79 was associated with CCA progression and metastasis, indicating that it is a poor prognostic marker for CCA. In conclusion, as both antibodies resulted in mirror-image staining, the involve- ment of G8-144 and MECA-79 in O-glycan synthesis could be considered as potential favorable and unfavorable biomarkers, respectively, for CCA prognosis.