BMC Cancer (Jan 2009)

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

  • Shaha Ashok R,
  • Patel Snehal,
  • Kraus Dennis H,
  • Boyle Jay O,
  • Ramanathan Yegnanarayana,
  • Yonekawa Yoshihiro,
  • Williams Tijaana,
  • Ghossein Ronald,
  • Carlson Diane L,
  • Socci Nicholas D,
  • Talbot Simon,
  • O-charoenrat Pornchai,
  • Estilo Cherry L,
  • Wong Richard J,
  • Huryn Joseph M,
  • Shah Jatin P,
  • Singh Bhuvanesh

DOI
https://doi.org/10.1186/1471-2407-9-11
Journal volume & issue
Vol. 9, no. 1
p. 11

Abstract

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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 (PMMP-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 (PHSAL2 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.