Differential Gene Expression in Normal Skin, Actinic Keratosis, and Squamous Cell Carcinoma
SH Ra, DS Cassarino, XM Li, SW Binder. UCLA Medical Center, Los Angeles, CA
Background: Squamous cell carcinoma (SCC) is one of the most commonly diagnosed skin malignancies. However, several lesions clinically and histologically simulate cutaneous SCC, including actinic keratosis (AK), which poses a challenge to the clinical diagnosis. The goal of our study was to develop a gene expression-based diagnostic method to distinguish among SCC, AK, and normal skin.
Design: Five actinic keratoses, five squamous cell carcinomas, and five normal skins were used for gene expression profiling. RNA was extracted from the paraffin blocks and converted to the labeled cRNA targets for human U133plus2.0 array hybridizations. The data analyses were performed using DNA-Chip Analyzer (D-Chip). Thresholds for selecting significant genes were set at a relative difference >= 2-fold, absolute difference > 100 signal intensity units and p<0.05. Genes that simultaneously met all three criteria were considered as significant changes.
Results: Over 200 genes were differentially expressed between SCC and normal skin and between AK and normal skin. The majority of the differentially expressed genes were down-regulated. Although overall gene expression profile of AK is similar to that of SCC, a small group of signature genes were identified which can be potentially useful for clinical discrimination (see Table I, FC= Fold change).
Table I. Differential gene expression between normal skin, AK, and SCC
|Sample||Total # of genes upregulated (>2FC)||Selected upregulated genes (FC)||Total # of genes downregulated (>2FC)||Selected downregulated genes (FC)|
|Normal skin vs. SCC||57||S100A7A, SERPINB13 (>5FC)||271||SCARA5, HBB, SCGB2A2, DCD (>60FC)|
|Normal skin vs. AK||21||S100A8, CCL18, CENTG3 (>4FC)||185||CNN1, SCGB2A2, DCD (>200FC)|
|AK vs. SCC||4||HOXC6, HOXC4 (>2.5FC)||8||NFIB, RPF6, RTN4 (>2FC)|
Conclusions: The distinctive gene expression profile of the selected squamous lesions offers the ability to distinguish SCC from its simulants. This offers the possibility of utilizing the gene expression microarray as a future molecular diagnostic tool to distinguish between normal skin, preneoplastic conditions such as AK, and SCC. In addition, the differentially expressed genes could be potentially used as prognostic markers or targets for future treatment.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 80, Monday Morning