title: A prospective proteomic-based study for identifying potential biomarkers for the diagnosis of cholangiocarcinoma.
abstract: BACKGROUND
  Cholangiocarcinoma (CCA) is becoming a common fatal hepatic tumor. Early detection of CCA is hampered by the absence of a sufficiently accurate and noninvasive diagnostic test. Proteomic analysis would be a powerful tool to identify potential biomarkers of this cancer.
  
  
  OBJECTIVE
  This study aims to identify new protein markers that are specific for CCA using proteomic approaches and to evaluate the performance of S100 calcium-binding protein A9 (S100A9) and chaperonin-containing TCR1, subunit 3 (CCTγ) as diagnostic markers for screening test of CCA.
  
  
  METHODS
  Two-dimensional differential gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were used to analyze and screen biomarker candidates in the proteomes of five human CCA samples and five healthy control samples. Subsequently, two potential biomarkers, S100A9 and CCTγ, were chosen for validation and analysis by immunohistochemical methods using CCA tissue microarrays.
  
  
  RESULTS
  Twenty protein spots were significantly elevated and five protein spots were downregulated in all patients (p < 0.05). The positive rate was significantly higher in patients with CCA (48 ± 35%) compared with the normal liver control group (5 ± 10%, p < 0.001), the hepatocellular carcinoma group (15 ± 20%, p < 0.001), and the cirrhosis group (12 ± 16%, p < 0.001). A greater proportion of patients with CCA were positive for CCTγ (72 ± 18%) compared with the normal liver control group (43 ± 22%, p < 0.001), the hepatocellular carcinoma group (45 ± 20%, p < 0.001), and the cirrhosis group (39 ± 25%, p < 0.001).
  
  
  CONCLUSIONS
  Combined comparative proteomic analysis using 2-D DIGE and MALDI-TOF is an effective method for identifying differentially expressed proteins in CCA tissues. The expression of S100A9 and CCTγ showed promise as novel diagnostic markers for CCA.
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er RD, Shanghai, 200025, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shi
authors.forename: Xiaxing
authors.initials: X
authors.lastname: Deng
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.forename: Baiyong
authors.initials: B
authors.lastname: Shen
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Jin
authors.forename: Zhecheng
authors.initials: Z
authors.lastname: Zhu
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Chenghong
authors.initials: C
authors.lastname: Peng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism*; D016022:Case-Control Studies; D056404:Chaperonin Containing TCP-1 / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D040901:Proteomics; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D046888:Tissue Array Analysis; D057825:Two-Dimensional Difference Gel Electrophoresis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C533299:CCT3 protein, human; D040502:Calgranulin B; D056404:Chaperonin Containing TCP-1