Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors (<or=2 cm)

J Proteome Res. 2010 Apr 5;9(4):1923-30. doi: 10.1021/pr901085z.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cohort Studies
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Liver Neoplasms / blood*
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Proteomics / methods*
  • Sensitivity and Specificity
  • Vimentin / blood*

Substances

  • Biomarkers, Tumor
  • Vimentin