Microarray Analysis of Cutaneous Squamous Cell Carcinomas Reveals Enhanced Expression of Epidermal Differentiation Complex Genes
Microarray Analysis of Cutaneous Squamous Cell Carcinomas Reveals Enhanced Expression of Epidermal Differentiation Complex Genes
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DOI：
10.1002/mc.20636
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发表时间：
2010-07-01
影响因子：
4.6
通讯作者：
Kusewitt, Donna F.
中科院分区：
文献类型：
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作者：
Hudson, Laurie G.;Gale, James M.;Kusewitt, Donna F.
确定了从非免疫抑制患者的阳光照射部位取出的 12 例皮肤鳞状细胞癌 (SCC) 的基因表达谱。使用 Affymetrix HGU133 2.0 PlusGeneChip 将每个 SCC 中的基因表达与同一患者暴露在阳光下的皮肤中的基因表达进行比较。我们鉴定出 440 个基因在 SCC 中表达增加，738 个基因表达减少；总体而言，我们发现了基因表达的大量微小变化，而不是一些区分 SCC 和阳光照射皮肤的显着变化。根据使用 DAVID 的生物功能途径、使用 oPOSSUM 的转录控制元件以及使用 GSEA 的染色体定位来分析这个强大的数据集，提出了 SCC 中基因表达调控的遗传和表观遗传机制。 SCC中基因表达的一些改变模式与许多发育上重要的转录因子（叉头、HMG和同源因子）对空间分离基因的调节一致，这些转录因子负向调节基因表达，并且与一些正向调节表达的因子（Creb-1、NF kappa B、RelA和Sp-1）一致。我们还发现染色体 1q21 上表皮分化复合体基因的协调增强表达是 SCC 的一个标志。我们研究的一个新发现是鳞状细胞癌中角蛋白 13 的表达增强，这一结果通过鳞状细胞癌肿瘤组织阵列的免疫组织化学染色得到验证。 (c) 2010 Wiley-Liss, Inc.
Gene expression profiles were determined for 12 cutaneous squamous cell carcinomas (SCC) removed from sun-exposed sites on nonimmunosuppressed patients. Gene expression in each SCC was compared to that in sun-exposed skin from the same patient using the Affymetrix HGU133 2.0 PlusGeneChip. We identified 440 genes with increased expression in SCC and 738 with decreased expression; overall we identified a large number of small changes in gene expression rather than a few marked changes that distinguished SCC from sun-exposed skin. Analyzing this robust data set according to biofunctional pathways using DAVID, transcriptional control elements using oPOSSUM, and chromosomal location using GSEA suggested genetic and epigenetic mechanisms of gene expression regulation in SCC. Some altered patterns of gene expression in SCC were consistent with regulation of spatially separated genes by a number of developmentally important transcription factors (forkhead, HMG, and homeo factors) that negatively regulated gene expression and to a few factors that positively regulated expression (Creb-1, NF kappa B, RelA, and Sp-1). We also found that coordinately enhanced expression of epidermal differentiation complex genes on chromosome 1q21 was a hallmark of SCC. A novel finding in our study was enhanced expression of keratin 13 in SCC, a result validated by immunohistochemical staining of an SCC tumor tissue array. (c) 2010 Wiley-Liss, Inc.