Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma
Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma
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DOI：
10.1245/s10434-006-9226-2
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发表时间：
2007-04-01
影响因子：
3.7
通讯作者：
Riker, Adam I.
中科院分区：
文献类型：
--
作者：
Jensen, Eric H.;Lewis, James M.;Riker, Adam I.
前言：细胞凋亡基因的下调与恶性黑色素瘤的发生发展密切相关。采用基因芯片技术比较正常皮肤与黑色素瘤(薄黑色素瘤和厚黑色素瘤)、结节病和远处转移的促凋亡基因表达。方法：手术切除16例患者，其中皮肤1例，薄黑色素瘤6例，厚黑色素瘤7例，结节病6例，远处转移瘤8例。利用Affymetrix基因芯片(54,000个遗传元件，U133A+B…)分离RNA并进行微阵列分析。水平)被执行。计算样本组中每个基因的平均表达水平。然后比较不同组织组之间的表达谱。结果：我们回顾了54,000个遗传元素的表达，发现其中2,015个表达发生了显著变化。这代表了1602个基因。与正常皮肤相比，22个促凋亡基因被发现下调。将正常皮肤和转移皮肤进行比较，评估总体减少3.31-64.04倍。当按顺序比较组织类型时，当皮肤与所有黑色素瘤(薄黑色素瘤和厚黑色素瘤)进行比较时，基因表达的降幅最大(p=0.011)。亚集分析比较正常皮肤与薄黑色素瘤或厚黑色素瘤，发现从薄皮损到厚皮损的总体减少的最大成分(p=0.003)。结论：促凋亡基因的顺序下调与恶性黑色素瘤的进展有关。最大的褶皱减少发生在病变由薄变厚的过程中。
Introduction: Down-regulation of apoptosis genes has been implicated in the development and progression of malignant melanoma. We used cDNA microarray to evaluate pro-apoptotic gene expression comparing normal skin to melanoma (thin and thick), nodal disease and distant metastases.Methods: Twenty-eight specimens including skin (n = 1), thin melanoma (n = 6), thick melanoma (n = 7), nodal disease (n = 6), and distant metastases (n = 8), were harvested at the time of resection from 16 individuals. RNA was isolated and microarray analysis utilizing the Affymetrix GeneChip (54,000 genetic elements, U133A+B... levels) was performed. Mean level of expression was calculated for each gene within a sample group. Expression profiles were then compared between tissue groups. Student's t-test was used to determine variance in expression between groups.Results: We reviewed the expression of 54,000 genetic elements, of which 2,015 were found to have significantly altered expression. This represents 1,602 genes. Twenty-two pro-apoptotic genes were found to be down-regulated when compared to normal skin. Overall reduction was evaluated comparing normal skin to metastases with a range of 3.31-64.04-fold-decrease. When comparing the tissue types sequentially, the greatest fold-decrease in gene expression occurred when comparing skin to all melanomas (thin and thick) (p = 0.011). Subset analysis comparing normal skin to thin melanoma or thick melanoma, revealed the greatest component of overall reduction at the transition from thin to thick lesions (p = 0.003).Conclusion: Sequential down-regulation of pro-apoptotic genes is associated with the progression of malignant melanoma. The greatest fold-decrease occurs in the transformation from thin to thick lesions.