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BMC Cancer

, 9:11

First Online: 12 January 2009Received: 27 February 2008Accepted: 12 January 2009DOI: 10.1186-1471-2407-9-11

Cite this article as: Estilo, C.L., O-charoenrat, P., Talbot, S. et al. BMC Cancer 2009 9: 11. doi:10.1186-1471-2407-9-11

Abstract

BackgroundThe 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.

MethodsThe 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.

ResultsHierarchical 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. PACE4mRNA expression failed to show correlation with any of the relevant parameters.

ConclusionThe 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.

AbbreviationsSCCsquamous cell carcinoma

CGHcomparative genomic hybridization

RTreverse transcription

PCRpolymerase chain reaction

RRrisk ratio

CIconfidence intervals

ESTexpressed sequence tag.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-11 contains supplementary material, which is available to authorized users.

Cherry L Estilo, Pornchai O-charoenrat contributed equally to this work.

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Autor: Cherry L Estilo - Pornchai O-charoenrat - Simon Talbot - Nicholas D Socci - Diane L Carlson - Ronald Ghossein - Tijaana 

Fuente: https://link.springer.com/







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