Molecular classification of oral cancer by cDNA microarrays identifies overexpressed genes correlated with nodal metastasis

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 BTSYQ 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). BTSYQ 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, CLDNI 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. © 2004 Wiley-Liss, Inc.