Identification of tumor biomarkers to assist early diagnosis and monitoring of disease progression may potentially decrease the mortality and morbidity associated with oral cancer.
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.
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).
These results suggest that haptoglobin has a great potential as a sensitive plasma biomarker for early detection of patients with OSCC.
2-DE, 2-dimentional gel electrophoresis; 4-NQO, 4-nitroquinoline 1-oxide; OSCC, oral squamous cell carcinoma; Q-TOF, quadrupole-time of flight"