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皮肤鳞状细胞癌中失调基因的鉴定

Identification of dysregulated genes in cutaneous squamous cell carcinoma.

作者信息

Dang Chantip, Gottschling Marc, Manning Kizzie, O'Currain Eoin, Schneider Sylke, Sterry Wolfram, Stockfleth Eggert, Nindl Ingo

机构信息

Department of Dermatology, Charité, Skin Cancer Center Charité, University Hospital of Berlin, Berlin, Germany.

出版信息

Oncol Rep. 2006 Sep;16(3):513-9.

Abstract

Carcinogenesis is a multi-step process resulting from the accumulation of genetic mutations and subsequently leading to dysregulated genes, but the number and identity of differentially expressed genes in cutaneous squamous cell carcinoma (SCC) is unknown at present. In order to identify dysregulated genes, we examined the relative mRNA expression present in cutaneous SCC and its precursor lesion actinic keratosis (AK) by comparison to normal skin. Snap frozen biopsies from 20 specimens of normal skin, 10 AK, and 10 cutaneous SCC were examined. Total-RNA was extracted, reversely transcribed, and 14 genes were investigated using gene-specific intron-flanking primers and quantitative real-time reverse transcription PCR. Specificity was confirmed by sequencing of the PCR amplicons. Ten of 14 genes were significantly dysregulated in AK and/or cutaneous SCC by comparison to normal skin. The genes CNN2, COX4I1, COX5B, COX7C, CRLF3, CTSC, NDRG1, and LMNA showed increased expression in skin cancer (p < 0.02), while RPL15 and LGTN were down-regulated (p < 0.03). The genes differentially expressed during skin carcinogenesis may prove useful in order to understand the origin and progression of cutaneous SCC and for diagnostic approaches.

摘要

致癌作用是一个多步骤过程,由基因突变的积累导致,随后导致基因失调,但目前皮肤鳞状细胞癌(SCC)中差异表达基因的数量和身份尚不清楚。为了鉴定失调基因,我们通过与正常皮肤比较,检测了皮肤SCC及其前驱病变光化性角化病(AK)中存在的相对mRNA表达。检查了来自20个正常皮肤标本、10个AK和10个皮肤SCC的速冻活检组织。提取总RNA,进行逆转录,并使用基因特异性内含子侧翼引物和定量实时逆转录PCR研究14个基因。通过对PCR扩增子进行测序确认特异性。与正常皮肤相比,14个基因中有10个在AK和/或皮肤SCC中显著失调。基因CNN2、COX4I1、COX5B、COX7C、CRLF3、CTSC、NDRG1和LMNA在皮肤癌中表达增加(p < 0.02),而RPL15和LGTN表达下调(p < 0.03)。在皮肤致癌过程中差异表达的基因可能有助于理解皮肤SCC的起源和进展以及用于诊断方法。

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