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Examination of oral cancer biomarkers by tissue microarray analysis.

Choi, Peter and Jordan, C Diana and Mendez, Eduardo and Houck, John and Yueh, Bevan and Farwell, D Gregory and Futran, Neal and Chen, Chu (2008) Examination of oral cancer biomarkers by tissue microarray analysis. Archives of otolaryngology--head & neck surgery, 134 (5). pp. 539-546. ISSN 1538-361X

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OBJECTIVE: To validate the DNA microarray results on a subset of genes that could potentially serve as biomarkers of oral squamous cell carcinoma (OSCC) by examining their expression with an alternate quantitative method and by assessing their protein levels. DESIGN: Based on DNA microarray data from our laboratory and data reported in the literature, we identified 6 potential biomarkers of OSCC to investigate further. We used quantitative real-time polymerase chain reaction to examine expression changes of CDH11, MMP3, SPARC, POSTN, TNC, and TGM3 in OSCC and histologically normal control tissues. We further examined validated markers at the protein level by immunohistochemical analysis of OSCC tissue microarray sections. RESULTS: Quantitative real-time polymerase chain reaction analysis revealed upregulation of CDH11, SPARC, POSTN, and TNC gene expression and decreased TGM3 expression in OSCC tissue compared with control tissue; MMP3 was not found to be differentially expressed. In tissue microarray immunohistochemical analyses, SPARC (secreted protein, acidic, rich in cysteine), periostin, and tenascin C exhibited increased protein expression in tumor tissue compared with control tissue, and their expression was primarily localized within tumor-associated stroma rather than tumor epithelium. Conversely, transglutaminase 3 protein expression was found only within keratinocytes in control tissue and was significantly downregulated in cancer cells. CONCLUSIONS: Of 6 potential gene markers of OSCC, initially identified by DNA microarray analyses, differential expression of CDH11, SPARC, POSTN, TNC, and TGM3 were validated by quantitative real-time polymerase chain reaction. Differential expression and localization of proteins encoded by SPARC, POSTN, TNC, and TGM3 were clearly shown by tissue microarray immunohistochemical analysis.

Item Type: Article or Abstract
Additional Information: This article is available to subscribers only via the URl above.
DOI: 10.1001/archotol.134.5.539
PubMed ID: 18490578
PMCID: PMC2578846
Grant Numbers: R01 CA 095419-01A1, T32 DC00018-26
Keywords or MeSH Headings: Cadherins/metabolism; Carcinoma, Squamous Cell/genetics/metabolism/pathology; Case-Control Studies; Cell Adhesion Molecules/metabolism; Cells, Cultured; Humans; Immunohistochemistry; Linear Models; Matrix Metalloproteinase 3/metabolism; Mouth Neoplasms/genetics/metabolism/pathology; Oligonucleotide Array Sequence Analysis; Osteonectin/metabolism; Reproducibility of Results; Tenascin/metabolism; Tissue Array Analysis; Transglutaminases/metabolism; Tumor Markers, Biological/genetics/metabolism;
Subjects: Research Methodologies > Genomics > Arrays
Research Methodologies > Genomics > Molecular Markers
Diseases > Solid tumors
Depositing User: Library Staff
Date Deposited: 02 Oct 2008 21:34
Last Modified: 14 Feb 2012 14:42

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