| Abstract: |
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. © 2009 Estilo et al; licensee BioMed Central Ltd. |
| Keywords: |
adult; cancer survival; clinical article; controlled study; aged; aged, 80 and over; middle aged; unclassified drug; overall survival; genetics; histopathology; cancer recurrence; squamous cell carcinoma; disease free survival; cancer staging; methodology; lymph node metastasis; gene overexpression; reverse transcription polymerase chain reaction; proteasome; gene expression profiling; tumor volume; transforming growth factor beta; tumor markers, biological; transcription factor; tumor antigen; tumor marker; prediction; transcription factors; cancer invasion; gene expression regulation; gene expression regulation, neoplastic; serine proteinase; serine endopeptidases; evaluation; messenger rna; microarray analysis; oligonucleotide array sequence analysis; gene identification; nucleotide sequence; glutathione transferase; dna microarray; ceramide glucosyltransferase; fatty acid binding protein; glucose transporter 3; guanine nucleotide binding protein; histone h2a; histone h2b; hypoxia inducible factor 1alpha; initiation factor 3; initiation factor 4a; interstitial collagenase; lipocortin 2; myosin; nicotinamide adenine dinucleotide (phosphate) transhydrogenase; oligonucleotide; phosphoglycerate mutase; phospholipase a2; platelet derived endothelial cell growth factor; proprotein convertase 4; protein hsal 2; pyridoxal kinase; small nuclear ribonucleoprotein; thymosin; zinc finger protein; pcsk6 protein, human; sall2 protein, human; slc2a3 protein, human; glossectomy; mouth mucosa; tongue cancer; unindexed sequence; tongue tumor; glucose transporter type 3; proprotein convertases; tongue neoplasms
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