Abstract A19: S100A7, a prognosticator and early predictive marker for head and neck/oral squamous cell carcinoma

Abstract

Abstract Recently using multidimensional LC-MS/MS with iTRAQ-tagging, we identified a panel of potential Head and Neck/Oral Squamous cell carcinoma (HNOSCC) biomarkers. S100A7 was one of the promising candidate biomarkers in this panel. S100A7 is 11.4 kDa calcium-binding protein of S100 protein family, found to be highly expressed in pre-invasive ductal carcinoma in situ of the breast. Here, we firstly report its potential as a prognostic biomarker for HNOSCC. The present study also further explores the clinical significance of S100A7 in identification of oral leukoplakic lesions in early stages. Ninety-nine HNOSCCs, 100 leukoplakias and 50 non-malignant archived tissues were retrieved from the research tissue bank to determine the expression of psoriasin using immunohistochemistry. The immunohistochemical data were subjected to statistical analyses using the SPSS 13.0 software (Chicago). Sensitivity and specificity were calculated and quantified using receiver operating characteristic (ROC) analysis. The expression of S100A7 in oral lesions was further validated by immunoblotting and RT-PCR analyses in the same tissue samples as used for immunohistochemical analysis. S100A7 expression was found to be significantly increased from normal mucosa to leukoplakia with or without dysplasia to HNOSCC (ptrend<0.001). Receiver Operating Characteristic (ROC) analysis was used to determine the potential of S100A7 as a biomarker for diagnosis of leukoplakia and OSCC. The area-under-the-curve (AUC) value was 0.732 and 0.843 for leukoplakia and OSCC respectively. S100A7 overexpression was significantly associated with dedifferentiation of tumors also. Cytoplasmic S100A7 was significantly associated with tumor size (p=0.015) and stage (p=0.023) of HNOSCC patients. In univariate analysis, nuclear localization of S100A7 was found to be associated poor survival (p < 0.014), while multivariate analysis revealed nuclear S100A7 as independent indicator of disease free survival (hazard ratio, 2.7; 95% confidence interval, 1.4–5.3; p < 0.004). This is the first large-scale study that suggests overexpression of S100A7 to be an early event and a poor prognostic factor in HNOSCC progression. On the basis of our current findings, S100A7 may serve as a potential biomarker in diagnosis and prognosis of HNOSCCs. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A19.