title: Identification by differential tissue proteome analysis of talin-1 as a novel molecular marker of progression of hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is characterized by a multistage process of tumor progression. This study addressed its molecular features to identify novel protein candidates involved in HCC progression.
  
  
  METHODS
  Using liquid chromatography-tandem mass spectrometry, proteomes of 4 early HCCs and 4 non-HCC tissues derived from 2 cases of liver transplant surgery were compared with respect to the separation profiles of their tryptic peptides. Immunohistochemistry was performed on 106 HCC nodules to confirm the results of the proteomic analysis.
  
  
  RESULTS
  Statistical analysis of the profiles selected the peptide peaks differentiating HCC from non-HCC. A database search of the tandem mass spectrometry data from those peptide peaks identified 61 proteins, including a cytoskeletal protein, talin-1, as upregulated in HCC. Talin-1 expression levels in HCC nodules were significantly associated with the dedifferentiation of HCC (p = 0.001). A follow-up survey of the examined clinical cases revealed a correlation between talin-1 upregulation and a shorter time to recurrence after resection (p = 0.039), which may be related to the higher rate of portal vein invasion in HCCs with talin-1 up-regulation (p = 0.029).
  
  
  CONCLUSIONS
  Proteomic analysis led to identification of talin-1 as a promising HCC marker. Talin-1 upregulation is associated with HCC progression and may serve as a prognostic marker.
authors.affiliation: Department of Gastroenterology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, Spain.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kanamori
authors.forename: Takao
authors.initials: T
authors.lastname: Kawakami
authors.forename: Kathryn
authors.initials: K
authors.lastname: Effendi
authors.forename: Ken
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Ebinuma
authors.forename: Yohei
authors.initials: Y
authors.lastname: Masugi
authors.forename: Wenlin
authors.initials: W
authors.lastname: Du
authors.forename: Keiko
authors.initials: K
authors.lastname: Nagasaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogiwara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kyono
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanabe
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Saito
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000737:chemistry*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D011379:Prognosis; D040081:Protein Array Analysis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D016608:Talin / Q000032:analysis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome; C518832:TLN1 protein, human; D016608:Talin