Gene expression patterns of normal human skin, actinic keratosis, and squamous cell carcinoma: a spectrum of disease progression.
OBJECTIVE
To identify and compare the gene expression profiles of actinic keratosis (AK) and squamous cell carcinoma (SCC) and to further clarify critical genetic alterations in the evolution of SCC from normal sun-damaged human skin.


METHODS
Observational study.


METHODS
University practice.


METHODS
Skin biopsy specimens were obtained from 16 patients. The specimens included 14 normal non-sun-exposed skin samples, 14 normal sun-exposed skin samples, 5 AKs, and 15 cutaneous SCCs.


METHODS
Gene expression profiles from normal non-sun-exposed skin, normal sun-exposed skin, AKs, and SCCs.


RESULTS
Using a highly astringent shrunken centroid threshold of 6.52 and the prediction analysis of microarrays, we identified 89 unique genes that most likely contribute to the molecular evolution of SCC. Our model was cross-validated using data from a separate study and clearly distinguishes between skin tumors (AK and SCC) and normal skin independent of sun exposure. Genes that were upregulated in AK and SCC were downregulated in normal skin, and genes that were downregulated in AK and SCC were upregulated in normal skin.


CONCLUSIONS
The finding of similar differentially expressed genes in AK and SCC confirms that AK is a precursor lesion of SCC and indicates that they are closely related genetically. Clear elucidation of these relationships will be critical to improving therapeutic approaches.
Department of Dermatology, School of Medicine and Cancer Research Center, University of New Mexico, Albuquerque, NM, USA.
R Steven
RS
Padilla
Sheldon
S
Sebastian
Zeyu
Z
Jiang
Ingo
I
Nindl
Richard
R
Larson
D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D055623:Keratosis, Actinic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012313:RNA / Q000235:genetics*; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D012313:RNA