Molecular classification of oral cancer by cDNA microarrays identifies overexpressed genes correlated with nodal metastasis
Open Access
- 26 May 2004
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 110 (6) , 857-868
- https://doi.org/10.1002/ijc.20197
Abstract
Our purpose was to classify OSCCs based on their gene expression profiles, to identify differentially expressed genes in these cancers and to correlate genetic deregulation with clinical and histopathologic data and patient outcome. After conducting proof‐of‐principle experiments utilizing 6 HNSCC cell lines, the gene expression profiles of 20 OSCCs were determined using cDNA microarrays containing 19,200 sequences and the BTSVQ method of data analysis. We identified 2 sample clusters that correlated with the T3‐T4 category of disease (p = 0.035) and nodal metastasis (p = 0.035). BTSVQ analysis identified a subset of 23 differentially expressed genes with the lowest QE scores in the cluster containing more advanced‐stage tumors. Expression of 6 of these differentially expressed genes was validated by quantitative real‐time RT‐PCR. Statistical analysis of quantitative real‐time RT‐PCR data was performed and, after Bonferroni correction, CLDN1 overexpression was significantly correlated with the cluster containing more advanced‐stage tumors (p = 0.007). Despite the clinical heterogeneity of OSCC, molecular subtyping by cDNA microarray analysis identified distinct patterns of gene expression associated with relevant clinical parameters. Application of this methodology represents an advance in the classification of oral cavity tumors and may ultimately aid in the development of more tailored therapies for oral carcinoma.Keywords
Funding Information
- National Cancer Institute of Canada (013220)
- Natural Sciences and Engineering Research Council of Canada (203833)
- Institute for Robotics and Intelligent Systems
- Wharton Fund
- Temmy Letner Fund
This publication has 48 references indexed in Scilit:
- Molecular cytogenetic analysis of head and neck squamous cell carcinoma: By comparative genomic hybridization, spectral karyotyping, and expression array analysisHead & Neck, 2002
- Identification of genes associated with head and neck carcinogenesis by cDNA microarray comparison between matched primary normal epithelial and squamous carcinoma cellsOncogene, 2002
- Genetic differences detected by comparative genomic hybridization in head and neck squamous cell carcinomas from different tumor sites: construction of oncogenetic trees for tumor progressionGenes, Chromosomes and Cancer, 2002
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Oral cancer in vivo gene expression profiling assisted by laser capture microdissection and microarray analysisOncogene, 2001
- Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assaysJournal of Molecular Endocrinology, 2000
- Distinct pattern of expression of differentiation and growth-related genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arraysOncogene, 2000
- Genomic-scale gene expression profiling of normal and malignant immune cellsCurrent Opinion in Immunology, 2000
- Distinct types of diffuse large B-cell lymphoma identified by gene expression profilingNature, 2000
- Mapping of the Gene Encoding the Regulatory Subunit RIIα of cAMP-Dependent Protein Kinase (Locus PRKAR2A) to Human Chromosome Region 3p21.3–p21.2Genomics, 1998