Yu Mei, Zloty David, Cowan Bryce, Shapiro Jerry, Haegert Anne, Bell Robert H, Warshawski Larry, Carr Nicholas, McElwee Kevin J
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
J Invest Dermatol. 2008 Jul;128(7):1797-805. doi: 10.1038/sj.jid.5701243. Epub 2008 Jan 17.
Basal-cell carcinoma (BCC), the most common neoplasm in humans, occurs in a variety of morphological presentations. The mechanisms of BCC development downstream of the initial genetic mutations are not well understood, and different BCC morphological presentations might exhibit distinct gene expression patterns. We investigated superficial (n=8), nodular (n=8), and morpheiform (n=7) BCCs using 21K cDNA microarrays. Global gene expression profiles between respective BCC subtypes, and as compared with normal skin (n=8), were statistically defined by significance analysis of microarrays (SAM). Thirty-seven genes were subsequently validated by quantitative reverse transcriptase-PCR analysis using an expanded set of 31 BCCs. Gene ontology analysis indicated that gene expression patterns of BCC subtypes in multiple biological processes showed significant variation, particularly in genes associated with the mitogen-activated protein kinase (MAPK) pathway. Notably, genes involved in response to DNA-damage stimulus were uniquely upregulated in morpheiform BCCs. Our results indicate a relative similarity in gene expression between nodular and superficial BCC subtypes. In contrast, morpheiform BCCs are more diverse, with gene expression patterns consistent with their more "invasive" phenotype. These data may help us understand the complex behavior of BCC subtypes and may eventually lead to new therapeutic strategies.
基底细胞癌（BCC）是人类最常见的肿瘤，有多种形态表现。初始基因突变下游的BCC发生机制尚不清楚，不同的BCC形态表现可能呈现出不同的基因表达模式。我们使用21K cDNA微阵列研究了浅表型（n = 8）、结节型（n = 8）和浸润型（n = 7）基底细胞癌。通过微阵列显著性分析（SAM）对各BCC亚型之间以及与正常皮肤（n = 8）相比的整体基因表达谱进行了统计学定义。随后，使用一组扩大至31个的BCC样本，通过定量逆转录聚合酶链反应分析验证了37个基因。基因本体分析表明，BCC亚型在多个生物学过程中的基因表达模式存在显著差异，特别是在与丝裂原活化蛋白激酶（MAPK）途径相关的基因中。值得注意的是，参与DNA损伤刺激反应的基因在浸润型BCC中独特地上调。我们的结果表明结节型和浅表型BCC亚型之间在基因表达上相对相似。相比之下，浸润型BCC更为多样，其基因表达模式与其更“侵袭性”的表型一致。这些数据可能有助于我们理解BCC亚型的复杂行为，并最终可能带来新的治疗策略。
