| Background: Cholangiocarcinoma (CC) is an intractable cancer, arising from biliaryepithelial cells, which has a poor prognosis and is increasing in incidence. Earlydiagnosis of CC is essential as surgical resection remains the only effective therapy.The purpose of this study was to identify improved biomarkers to facilitate earlydiagnosis and prognostication in CC. Methods: A comparative expression profile ofhuman bile samples from patients with cholangitis and CC was constructed using aclassic2D/MS/MS strategy and the expression of selected proteins was confirmed byWestern blotting. Immunohistochemistry was performed to determine the expressionlevels of selected candidate biomarkers in CC and matched normal tissues. Thespermatogenesis associated20(SSP411; also named SPATA20) was then quantifiedin serum samples using an ELISA. Finally, we studied the role of SSP411involved inthe tumorigenesis of CC via the cell line of HuCCA-1. Results: We identified97differentially expressed protein spots, corresponding to49different genes, of which38were upregulated in bile from CC patients. Western blotting confirmed thatphosphoglycerate mutase1(brain)(PGAM-1), protein disulfide isomerase family A,member3(PDIA3), heat shock60kDa protein1(chaperonin)(HSPD1) and SSP411were significantly upregulated in individual bile samples from CC patients.Immunohistochemistry demonstrated these proteins were also overexpressed in CC,relative to normal tissues. SSP411displayed value as a potential serum diagnosticbiomarker for CC, with a sensitivity of90.0%and specificity of83.3%at a cutoffvalue of0.63. The proliferation and invasion ability of cholangiocarcinoma cells wereinhibited when SSP411was knocked down by ShRNA against SSP411. Conclusions:We successfully constructed a proteomic profile of CC bile proteins, providing avaluable pool novel of candidate biomarkers. SSP411has potential as a biomarker forthe diagnosis and molecular therapy target of CC. |
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