Abstract
BackgroundSkin cancer accounts for 1/3 of all newly diagnosed cancer. Although seldom fatal, basal cell carcinoma (BCC) is associated with severe disfigurement and morbidity. BCC has a unique interest for researchers, as although it is often locally invasive, it rarely metastasises. This paper, reporting the first whole genome expression microarray analysis of skin cancer, aimed to investigate the molecular profile of BCC in comparison to non-cancerous skin biopsies. RNA from BCC and normal skin specimens was analysed using Affymetrix whole genome microarrays. A Welch t-test was applied to data normalised using dCHIP to identify significant differentially-expressed genes between BCC and normal specimens. Principal component analysis and support vector machine analysis were performed on resulting genelists, Genmapp was used to identify pathways affected, and GOstat aided identification of areas of gene ontology more highly represented on these lists than would be expected by chance.ResultsFollowing normalisation, specimens clustered into groups of BCC specimens and of normal skin specimens. Of the 54,675 gene transcripts/variants analysed, 3,921 were differentially expressed between BCC and normal skin specimens. Of these, 2,108 were significantly up-regulated and 1,813 were statistically significantly down-regulated in BCCs.ConclusionFunctional gene sets differentially expressed include those involved in transcription, proliferation, cell motility, apoptosis and metabolism. As expected, members of the Wnt and hedgehog pathways were found to be significantly different between BCC and normal specimens, as were many previously undescribed changes in gene expression between normal and BCC specimens, including basonuclin2 and mrp9. Quantitative-PCR analysis confirmed our microarray results, identifying novel potential biomarkers for BCC.
Highlights
Skin cancer accounts for 1/3 of all newly diagnosed cancer
It is estimated that the incidence of cutaneous basal cell carcinoma is increasing worldwide by up to 10% per year [1] and it currently accounts for approximately 80% of all non-melanoma skin cancer – with highest rates in elderly men and increasing incidence in young women [2]
In order to increase our understanding of the molecular events involved in the development/expression of basal cell carcinoma (BCC), here we report our findings from whole genome microarray analysis of BCC and normal skin specimens
Summary
Basal cell carcinoma (BCC) is associated with severe disfigurement and morbidity. It is estimated that the incidence of cutaneous basal cell carcinoma is increasing worldwide by up to 10% per year [1] and it currently accounts for approximately 80% of all non-melanoma skin cancer – with highest rates in elderly men and increasing incidence in young women [2]. Several sub-types of BCC have been identified These include nodular-ulcerated BCC (the most frequently occurring type; often with ulceration ("rodent ulcer")); superficial BCC (often multiple); sclerosing BCC (cancer cells surrounded by dense fibrosis and so resemble scars; highest recurrence rate of BCCs after treatment); cystic BCC (uncommon; tumour undergoes central degradation to form a cystic lesion); linear BCC (recently recognised clinical entity with increased risk for aggressive histopathology); and micronodular BCC (small tumour nests; often with subclinical growth). Genes reported to be associated with susceptibility to BCC include CYP2D6, GST-T1, vitamin D receptor, and TNF; with UVB irradiaton known to cause mutations in the p53 tumour suppressor gene, leading to the development of this cancer [1]
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