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Analysis of the gene expression profile in normal human epidermal keratinocytes and cutaneous squamous cell carcinoma cell lines

ABSTRACT: The incidence of keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC) is increasing worldwide making it the second most common metastatic skin cancer. We used microarrays to characterize gene expression profile in normal human epidermal keratinocytes (NHEK) and cSCC cell lines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66359 | GEO | 2015/08/27

SECONDARY ACCESSION(S): PRJNA276661

REPOSITORIES: GEO

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Analysis of the gene expression profile in normal human epidermal keratinocytes and cutaneous squamous cell carcinoma cell lines

Project description:The incidence of keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC) is increasing worldwide making it the second most common metastatic skin cancer. We used microarrays to characterize gene expression profile in normal human epidermal keratinocytes (NHEK) and cSCC cell lines. Total RNAs from normal human epidermal keratinocytes (n=5) and cSCC cell lines (n=8) were extracted. The samples were processed for Affymetrix 3´ IVT Express Kit according to manufacture’s protocol.

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Project description:Cutaneous squamous cell carcinoma (cSCC) is the most prominent tumor of non-melanoma skin cancers and the most aggressive tumor among keratinocyte carcinoma of the skin, showing a high potential for local invasion and metastasis. The cSCC incidences increased dramatically in recent years and the disease occurs more commonly than any other malignancy. The secretome of cancer cells is currently the focus of many studies in order to identify new marker proteins for different types of cancer and to investigate its influence on the tumor microenvironment. In our study we evaluated whether the secretome of cSCC cells has an impact on keratinocytes, the surrounding tissue cells of cSCC. Therefore, we analyzed and compared the secretome of human A431 cancer cells and of HaCaT keratinocytes by mass spectrometry.

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Project description:Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer type and arises from keratinocytes. Most cSCC progress from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain only partially understood. Here we have used Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status of about 850.000 CpGs in epidermal preparations from healthy skin, AK and cSCC. Importantly, we found that the premalignant AK samples displayed classical features of cancer methylomes and were highly similar to cSCC methylomes. Further analysis identified typical features of stem cell methylomes, such as a reduced DNA methylation age, non-CpG methylation and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature was detected only in one half of the AK and cSCC samples, while the other half showed methylation patterns that were more closely related to the control epidermis. These findings suggest the existence of two distinct subclasses of AK and cSCC that originate from distinct keratinocyte differentiation stages.

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