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Background  The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling.    Methods  The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes,  GLUT3 ,  HSAL2 , and  PACE4 , were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR.    Results  Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes,  MMP-1  encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of  GLUT3 ,  HSAL2  and  PACE4 , respectively. Univariate analyses demonstrated that  GLUT3  over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038).   HSAL2  was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047).   In survival studies, only  GLUT3  showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003).  PACE4  mRNA expression failed to show correlation with any of the relevant parameters.Conclusion  The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.

Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis