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

ABSTRACT: 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.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.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.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.

SUBMITTER: Estilo CL

PROVIDER: S-EPMC2649155 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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

Estilo Cherry L CL O-charoenrat Pornchai P Talbot Simon S Socci Nicholas D ND Carlson Diane L DL Ghossein Ronald R Williams Tijaana T Yonekawa Yoshihiro Y Ramanathan Yegnanarayana Y Boyle Jay O JO Kraus Dennis H DH Patel Snehal S Shaha Ashok R AR Wong Richard J RJ Huryn Joseph M JM Shah Jatin P JP Singh Bhuvanesh B

BMC cancer 20090112

<h4>Background</h4>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.<h4>Methods</h4>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 diseas ...[more]

PMID: 19138406

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Project description: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. 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). The 20 patients were then 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 by quantitative real-time RT-PCR. Results: 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=0.0467). In survival studies, only GLUT3 showed a prognostic value with disease-specific (P=0.049), relapse-free (P-0.0042) and overall survival (P=0.003). PACE4 mRNA expression failed to show correlation with any of the relevant parameters. Conclusions: 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. Keywords: gene expression profiling The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. 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). The 20 patients were then 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 by quantitative real-time RT-PCR

Project description:BACKGROUND: Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF) are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties. RESULTS: We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT). We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1). We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC) of more than 2.0 (P<0.05). Among the 442 TF genes related to BPH-induced resistance, most of them were readily induced in TN1 than in RHT by BPH feeding, for instance, 154 TF genes were up-regulated in TN1, but only 31 TF genes were up-regulated in RHT at 24 hours after BPH infestation; 2-4 times more TF genes were induced in TN1 than in RHT by BPH. At an FC threshold of >10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT. CONCLUSIONS: We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants protect themselves by reducing their metabolic level to inhibit feeding by BPH and prevent damage from water and nutrient loss. We have selected 21 TF genes related to BPH resistance for further analyses to understand the molecular responses to BPH feeding in rice.

Dataset Information

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

Publications

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

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