title: 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 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.
authors.affiliation: Department of Cellular and Molecular Biology, Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Giles C
authors.initials: GC
authors.lastname: Warner
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Reis
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.forename: Mujahid
authors.initials: M
authors.lastname: Sultan
authors.forename: Shilpi
authors.initials: S
authors.lastname: Arora
authors.forename: Christina
authors.initials: C
authors.lastname: Macmillan
authors.forename: Antti A
authors.initials: AA
authors.lastname: Makitie
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
authors.forename: Nancy
authors.initials: N
authors.lastname: Reid
authors.forename: Mahadeo
authors.initials: M
authors.lastname: Sukhai
authors.forename: Jeremy
authors.initials: J
authors.lastname: Freeman
authors.forename: Patrick
authors.initials: P
authors.lastname: Gullane
authors.forename: Jonathan
authors.initials: J
authors.lastname: Irish
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction