Molecular classification of oral cancer by cDNA microarrays identifies overexpressed genes correlated with nodal metastasis.
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.
Warner
Giles C
GC
Department of Cellular and Molecular Biology, Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
Reis
Patricia P
PP
Jurisica
Igor
I
Sultan
Mujahid
M
Arora
Shilpi
S
Macmillan
Christina
C
Makitie
Antti A
AA
Grénman
Reidar
R
Reid
Nancy
N
Sukhai
Mahadeo
M
Freeman
Jeremy
J
Gullane
Patrick
P
Irish
Jonathan
J
Kamel-Reid
Suzanne
S
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