Chen, Chu and Méndez, Eduardo and Houck, John and Fan, Wenhong and Lohavanichbutr, Pawadee and Doody, Dave and Yueh, Bevan and Futran, Neal D. and Upton, Melissa and Farwell, D. Gregory and Schwartz, Stephen M. and Zhao, Lue Ping (2008) Gene expression profiling identifies genes predictive of oral squamous cell carcinoma. Cancer Epidemiology, Biomarkers & Prevention, 17 (8). pp. 2152-2162. ISSN 1538-7755
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Abstract
Oral squamous cell carcinoma (OSCC) is associated with substantial mortality and morbidity. To identify potential biomarkers for early detection of invasive OSCC, we compared gene expression of incident primary OSCC, oral dysplasia, and clinically normal oral tissue from surgical patients without head and neck cancer or pre-neoplastic oral lesions (controls), using Affymetrix U133 2.0 Plus arrays. We identified 131 differentially expressed probe sets using a training set of 119 OSCC patients and 35 controls. Forward and stepwise logistic regression analyses identified 10 successive combinations of genes which expression differentiated OSCC from controls. The best model included LAMC2, encoding laminin gamma 2 chain, and COL4A1, encoding collagen, type IV, alpha 1 chain. Subsequent modeling without these two markers showed that COL1A1, encoding collagen, type I, alpha 1 chain, and PADI1, encoding peptidyl arginine deiminase, type 1, also can distinguish OSCC from controls. We validated these two models using an internal independent testing set of 48 invasive OSCC and 10 controls and an external testing set of 42 head and neck squamous cell carcinoma (HNSCC) cases and 14 controls (GEO GSE6791), with sensitivity and specificity above 95%. These two models were also able to distinguish dysplasia (n=17) from control (n=35) tissue. Differential expression of these four genes was confirmed by qRT-PCR. If confirmed in larger studies, the proposed models may hold promise for monitoring local recurrence at surgical margins and the development of second primary oral cancer in OSCC patients.
| Item Type: | Article or Abstract |
|---|---|
| DOI: | 10.1158/1055-9965.EPI-07-2893 |
| PubMed ID: | 18669583 |
| NIHMSID: | NIHMS69787 |
| PMCID: | PMC2575803 |
| Grant Numbers: | R01CA095419-05, T32DC00018-26, K12RR023265-04 |
| Keywords or MeSH Headings: | Carcinoma, Squamous Cell/genetics* Case-Control Studies Collagen Type I/genetics Collagen Type IV/genetics Female Gene Expression Profiling* Gene Expression Regulation, Neoplastic Humans Hydrolases/genetics Laminin/genetics Logistic Models Male Microarray Analysis Models, Genetic Mouth Neoplasms/genetics* Neoplasm Recurrence, Local Reverse Transcriptase Polymerase Chain Reaction Sensitivity and Specificity Tumor Markers, Biological/genetics |
| Subjects: | Research Methodologies > Genomics > Arrays Research Methodologies > Genomics > Molecular Markers Diseases > Solid tumors Research Methodologies > Epidemiology |
| Depositing User: | authors@FHCRC Administrator-Import |
| Date Deposited: | 15 Sep 2008 19:49 |
| Last Modified: | 14 Feb 2012 14:42 |
| URI: | http://authors.fhcrc.org/id/eprint/32 |
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