title: Comparative proteomic profiling of human bile reveals SSP411 as a novel biomarker of cholangiocarcinoma.
abstract: BACKGROUND
  Cholangiocarcinoma (CC) is an intractable cancer, arising from biliary epithelial cells, which has a poor prognosis and is increasing in incidence. Early diagnosis of CC is essential as surgical resection remains the only effective therapy. The purpose of this study was to identify improved biomarkers to facilitate early diagnosis and prognostication in CC.
  
  
  METHODS
  A comparative expression profile of human bile samples from patients with cholangitis and CC was constructed using a classic 2D/MS/MS strategy and the expression of selected proteins was confirmed by Western blotting. Immunohistochemistry was performed to determine the expression levels of selected candidate biomarkers in CC and matched normal tissues. Finally, spermatogenesis associated 20 (SSP411; also named SPATA20) was quantified in serum samples using an ELISA.
  
  
  RESULTS
  We identified 97 differentially expressed protein spots, corresponding to 49 different genes, of which 38 were upregulated in bile from CC patients. Western blotting confirmed that phosphoglycerate mutase 1 (brain) (PGAM-1), protein disulfide isomerase family A, member 3 (PDIA3), heat shock 60 kDa protein 1 (chaperonin) (HSPD1) and SSP411 were significantly upregulated in individual bile samples from CC patients. Immunohistochemistry demonstrated these proteins were also overexpressed in CC, relative to normal tissues. SSP411 displayed value as a potential serum diagnostic biomarker for CC, with a sensitivity of 90.0% and specificity of 83.3% at a cutoff value of 0.63.
  
  
  CONCLUSIONS
  We successfully constructed a proteomic profile of CC bile proteins, providing a valuable pool novel of candidate biomarkers. SSP411 has potential as a biomarker for the diagnosis of CC.
authors.affiliation: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Weizhi
authors.initials: W
authors.lastname: Wang
authors.forename: Jindao
authors.initials: J
authors.lastname: Wu
authors.forename: Bing
authors.initials: B
authors.lastname: Feng
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Jincao
authors.initials: J
authors.lastname: Tang
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.forename: Liyong
authors.initials: L
authors.lastname: Pu
authors.forename: Qiyun
authors.initials: Q
authors.lastname: Tang
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Li
mesh_terms: D000368:Aged; D001646:Bile / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D013879:Thioredoxins