Gene expression profiling in squamous cell carcinoma of the oral cavity shows abnormalities in several signaling pathways.
OBJECTIVE
To examine gene expression profiles in squamous cell carcinoma of the oral cavity (oral SCC) compared with histologically matched normal tissue.


METHODS
Fresh-frozen tissue was prospectively obtained from individuals undergoing surgical resections for oral SCC.


METHODS
RNA was extracted from seven sets of oral SCC and matched normal tissue. Gene expression profiles were obtained by interrogation of Affymetrix Gene Chip Arrays with cRNA prepared from the tissue. Expression values were subjected to a paired t test. Genes that were judged to differ between oral SCC and normal tissue were annotated according to their name in the Affymetrix Netaffx database and according to their function as indicated by their Gene Ontology Consortium number.


RESULTS
Of the 10,599 probe sets that were analyzed, 523 genes were abnormally expressed in SCC of the head and neck (P < or = .01), and 417 of these genes were abnormally expressed in all seven tumors in the same manner. Hierarchical clustering of the 121 genes that were abnormally expressed in cancerous relative to normal tissue (P < or = .001) showed that the tissue segregated into two groups consisting of normal and transformed tissue, as expected. The abnormal expression of two genes that were up regulated in oral SCC (ADAM 12 and PTHLH) and two genes that were down-regulated in SCCHN (EMP-1 and P11) were confirmed by real-time polymerase chain reaction and immunohistochemistry (ADAM 12) using additional sets of tissue.


CONCLUSIONS
The data showed that oral SCC aberrantly express genes in cellular pathways related to proliferation, apoptosis, extracellular matrix degradation, adhesion, transforming growth factor-beta signaling, and transcription. Further work is needed to determine the role of these genes in the development and progression of oral SCC.
Kornberg
Lori J
LJ
Department of Otolaryngology, University of Florida College of Dentistry, Gainesville, Florida 32610, USA.
Villaret
Douglas
D
Popp
Michael
M
Lui
Li
L
McLaren
Rachel
R
Brown
Heather
H
Cohen
Donald
D
Yun
James
J
McFadden
Michael
M
D051722:ADAM Proteins; D000072199:ADAM12 Protein; D000368:Aged; D017306:Annexin A2 / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D009857:Oncogenes / Q000235:genetics; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics; D011446:Prospective Studies; D018075:RNA, Complementary; D012334:RNA, Neoplasm / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D009418:S100 Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation; D000099248:S100 Calcium Binding Protein A10
D051722:ADAM Proteins; D000072199:ADAM12 Protein; D017306:Annexin A2; D008565:Membrane Proteins; D008666:Metalloendopeptidases; D009363:Neoplasm Proteins; D044162:Parathyroid Hormone-Related Protein; D018075:RNA, Complementary; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C470121:PTHLH protein, human; C097051:epithelial membrane protein-1; C000606480:ADAM12 protein, human