Howell Brandon G, Solish Nowell, Lu Chao, Watanabe Hideaki, Mamelak Adam J, Freed Irwin, Wang Binghe, Sauder Daniel N
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0900, USA.
J Dermatol Sci. 2005 Jul;39(1):39-51. doi: 10.1016/j.jdermsci.2005.02.004. Epub 2005 Apr 18.
Basal cell carcinoma (BCC) is the most common human neoplasm. Much interest lies in determining the genetic basis of BCC to explain the unique locally invasive phenotype and infrequent metastatic behavior of these skin tumors.
We sought to examine a gene expression profile for BCC to elucidate new molecules responsible for its unique growth characteristics.
We analyzed gene expression patterns of 50 BCC tumors using spotted cDNA microarrays of 1718 characterized human genes related to cancer and immunity. This is the largest and most comprehensive gene expression study ever performed for BCC. Nodular and sclerosing histological subtypes of BCC were examined and compared to normal control skin. After statistical filtering, 374 significantly dysregulated genes were sorted by hierarchical clustering to determine trends of gene expression and similarities between patient gene expression profiles.
A total of 165 upregulated genes and 115 downregulated genes were identified. These covered a range of categories, including extracellular matrix, cell junctions, motility, metastasis, oncogenes, tumor suppressors, DNA repair, cell cycle, immune regulation and angiogenesis. Clusters of genes were either commonly dysregulated across the 50 patient sample, or selectively affected in subsets of tumors. Histological subtypes were not distinguishable by hierarchical clustering. Many of the genes elucidated, including collagen type IV subunits and other novel candidates, possess functions related to extracellular matrix remodeling and metastasis.
These results suggest a gene profile which may explain the invasive growth yet rarely metastatic behavior of BCC. The genes identified may also be potential targets for therapeutics aimed at further controlling invasiveness and local destruction of BCC.
基底细胞癌（BCC）是人类最常见的肿瘤。人们对确定BCC的遗传基础非常感兴趣，以解释这些皮肤肿瘤独特的局部侵袭性表型和罕见的转移行为。
我们试图检测BCC的基因表达谱，以阐明与其独特生长特征相关的新分子。
我们使用包含1718个与癌症和免疫相关的已表征人类基因的斑点cDNA微阵列，分析了50个BCC肿瘤的基因表达模式。这是有史以来针对BCC进行的最大规模、最全面的基因表达研究。对BCC的结节性和硬化性组织学亚型进行了检查，并与正常对照皮肤进行了比较。经过统计筛选后，通过层次聚类对374个显著失调的基因进行排序，以确定基因表达趋势以及患者基因表达谱之间的相似性。
共鉴定出165个上调基因和115个下调基因。这些基因涵盖了一系列类别，包括细胞外基质、细胞连接、运动性、转移、癌基因、肿瘤抑制因子、DNA修复、细胞周期、免疫调节和血管生成。基因簇要么在50个患者样本中普遍失调，要么在部分肿瘤亚组中受到选择性影响。通过层次聚类无法区分组织学亚型。所阐明的许多基因，包括IV型胶原亚基和其他新的候选基因，都具有与细胞外基质重塑和转移相关的功能。
这些结果提示了一种基因谱，可能解释BCC的侵袭性生长但很少转移的行为。所鉴定的基因也可能是旨在进一步控制BCC侵袭性和局部破坏的治疗方法的潜在靶点。
