| Abstract |
Cholangiocarcinoma (CCA), or cancer of the bile ducts, is primarily associated with infection with the liver
fluke Opisthorchis viverrini in northeast Thailand. The disease is associated with late presentation, poses
challenges for diagnosis and has a high mortality rate – features that highlight the need for tumor markers.
At present, there are no specific tumor markers that can indicate the early stages and status of CCA.
Proteomic analysis of the proteins expressed on the surface of tumor cells is particularly difficult since
proteome-wide analysis of surface membrane proteins has thus far been hampered by the lack of effective
strategies to profile hydrophobic membrane proteins. In this study, a sequential protein extraction
was utilized to overcome this problem. Membrane protein was extracted from four CCA cell lines with
different tumor forming capabilities. The non-tumor H69 biliary cell line was used as a control. Twodimensional-
PAGE followed by MALDI-TOF-MS was used to identify differentially expressed proteins.
Among 20 up-regulated membrane proteins identified in the CCA cell lines was ANXA2, a participant
in tumor invasion and metastasis in other cancers. Accordingly, ANXA2 was verified in human subjects
by probing, using a commercial anti-mouse monoclonal antibody and a tissue microarray of CCA (301
diagnosed cases), where it was found to associate with one of several tumor progression stages as
reflected by lymphatic invasion (P = 0.014) and metastasis (P = 0.026). Patients with high expression of
ANXA2 had a significantly shorter survival time (P = 0.011). ANXA2 expression in tumors may be useful
for predicting the poor outcome of CCA patients. |
Publication
Journal Publication
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