Background: Oral cancer is a serious health-care problem in several Asian countries.Methods: We used a carcinogen-induced mouse cancer model and mass spectrometry to identify potential biomarkers for the diagnosis or treatment of oral cancer. Two chemicals, 4-nitroquinoline 1-oxide (4-NQO) and arecoline (an extract of areca nut), in drinking water were used to induce oral squamous cell carcinoma in mice. Mass spectrometry analysis of sera sequentially collected from these mice showed that the level of several glycoproteins—including kininogen-1, thrombospondin-1, and leukaemia inhibitory factor receptor—was significantly elevated during early pathological changes of the tongue. Immunohistochemical staining showed kininogen-1 in the tumours of nine of 10 patients with oral cancer. We further collected tissue sections from 44 patients with T1/T2/N0 tumours, 35 patients with T1/T2/N+ tumours, 33 patients with T3/T4/N0 tumours, and 32 patients with T3/T4/N+ tumours, and determined the expression of kininogen-1 in the tumours by immunohistochemistry.Findings: Kininogen-1 is expressed in almost all tumours, and the percentage of tumour stained positive for kininogen-1 significantly increased from T1 to T2 stages. Increased kininogen-1 expression was seen in primary tumors of patients with large tumour and lymph node metastasis. Microarray analysis of gene expression between 40 pairs of human oral cancer specimens and adjacent normal specimens obtained from a different group of patients showed that the expression of kininogen-1 mRNA is substantially elevated in the tumours. mRNA expression of kininogen-1 and survival data from the 40 patients reveal that patients with tumours expressing a high level of kininogen-1 tend to have a shorter overall survival (Cox regression model analysis, p = 0.00051) and recurrence-free survival (p = 0.000575).Interpretation: Kininogen-1 could be a surrogate prognostic biomarker for patients with oral cancer.
Date:
2016-06
Relation:
European Journal of Cancer. 2016 Jun;603-615(Suppl. 1):e10.
