Potential Biomarkers For Biliary Tract Neoplasm And Its Molecular Mechanism

Biliary tract neoplasms are highly fatal diseases with poor prognosis. Curative treatment can only be expected from surgical resection of early stage tumors. However, the majority of patients initially present with advanced disease. To provide clues to find biomarkers for early diagnosis, prognosis and therapy, as well as to understand the molecular mechanisms governing cancer progression, use two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to screen differential protein profiles of these malignant and benign specimens. We identified51differentially expressed proteins at the level of bile, tissue and cell. Stathmin was found to be overexpressed in tumor cell lines RBE and GBC, Mrp14was found to be overexpressed in the tumor tissues of gallbladder cancer and extra-hepatic bile duct cancer, and in the bile of patients with malignant biliary tract tumours. Control-siRNA or Stathmin-siRNA were transfected to biliary tract cancer cell lines RBE and QBC939to make the stathmin expression at mRNA and protein level lowered, and then found that the cell migration of RBE and QBC939were significantly inhibited, and the expression of Stathmin levels positively correlated with the level of FAK phosphorylation. The results of confocal laser scanning microscope examination showed:in bile duct cancer cells, Stathmin and FAK co-located in the cytoplasm and cell membrane.In summary, we found the Stathmin upregulated at the mRNA and protein levels in the bile duct cancer. Overexpression of Stathmin enhanced the interaction of Stathmin and FAK, and promoted the effect of FAK phosphorylation, thus contributing to biliary tumor cell migration. So in the clinical treatment of biliary tract tumors, by inhibiting the expression or activity of stathmin, it could be one of the markers and therapeutic targets.