Proteomics-based identification of haptoglobin as a novel plasma biomarker in oral squamous cell carcinoma

Clin Chim Acta. 2010 Jul 4;411(13-14):984-91. doi: 10.1016/j.cca.2010.03.028. Epub 2010 Mar 30.

Abstract

Background: Identification of tumor biomarkers to assist early diagnosis and monitoring of disease progression may potentially decrease the mortality and morbidity associated with oral cancer.

Methods: A mouse model with oral squamous cell carcinoma (OSCC) induced by 4-nitroquinoline 1-oxide (4-NQO)/arecoline in drinking water was established to discover stage-associated biomarkers. A proteomics approach, immunoblot and immunohistochemical analysis were used to validate the expressed biomarkers in mice with OSCC. Human plasma samples were also collected and candidate biomarkers were evaluated using enzyme-linked immunosorbent assay.

Results: Proteomic profiling of mouse plasma samples indicated that haptoglobin and apolipoprotein A1 precursor were up-regulated in the mice with OSCC. Immunoblotting of plasma samples and immunohistochemical analysis of oral tissues showed a significantly higher level of haptoglobin in the OSCC mice than in the control mice. The expression of haptoglobin in human plasma samples from 52 patients with OSCC indicated a strong correlation between the increasing levels of haptoglobin and the clinical stages of OSCC (P<0.01).

Conclusions: These results suggest that haptoglobin has a great potential as a sensitive plasma biomarker for early detection of patients with OSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Carcinoma, Squamous Cell / blood*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Early Diagnosis
  • Female
  • Gene Expression Regulation, Neoplastic
  • Haptoglobins / metabolism*
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Mouth Neoplasms / blood*
  • Mouth Neoplasms / diagnosis
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Neoplasm Staging
  • Proteomics*
  • Tongue Neoplasms / blood
  • Tongue Neoplasms / diagnosis
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology

Substances

  • Biomarkers
  • Haptoglobins