title: Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors (<or=2 cm).
abstract: Small hepatocellular carcinomas (HCCs) can be effectively cured by surgery with good clinical outcomes. However, the conventional AFP marker is ineffective in detecting small tumors. Here we employed a proteomic profiling approach to identify a candidate marker for HCC (<or=2 cm) in tumor tissues and then evaluate its clinical feasibility in patients' sera. The study was divided into 2 phases. (i) Biomarker discovery: we collected 76 frozen liver tissues (40 HCC and 36 controls) for proteomics profiling. Candidate protein markers were identified by MALDI-TOF/TOF and confirmed by immunoblot and qPCR. (ii) Clinical evaluation: Selected biomarker was tested by ELISA for sensitivity and specificity using serum samples from a separate cohort of 152 subjects (88 HCC and 64 controls). Vimentin was found significantly overexpressed in HCC, in particular the small-size subgroup (<or=2 cm) with p < 0.01. When tested in the serum samples, vimentin level was significantly higher in small tumors than the non-neoplastic controls (AUC = 0.69 and p < 0.01). Further analysis suggested that elevated circulating vimentin level could detect small HCC at 40.91% sensitivity and 87.50% specificity. Moreover, vimentin was found to be superior to serum AFP assayed at different cut-offs in detecting small tumors. When combined with AFP, the detection sensitivity and specificity could be further enhanced to 58.77 and 98.15%, respectively. In conclusion, serum vimentin is a potential surrogate marker, either alone or in combination with AFP, for detection of small HCCs.
authors.affiliation: Department of Surgery, University of Hong Kong, Hong Kong, China.
authors.forename: Stella
authors.initials: S
authors.lastname: Sun
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: Nikki P
authors.initials: NP
authors.lastname: Lee
authors.forename: Chun
authors.initials: C
authors.lastname: Yeung
authors.forename: K L
authors.initials: KL
authors.lastname: Chan
authors.forename: Irene O L
authors.initials: IO
authors.lastname: Ng
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Day
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D014746:Vimentin / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D014746:Vimentin