High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma
High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma
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DOI：
10.1016/s0002-9440(10)65349-7
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发表时间：
1999-04-01
影响因子：
6
通讯作者：
Sauter, G
中科院分区：
文献类型：
--
作者：
Moch, H;Schraml, P;Sauter, G
肾细胞癌的发生发展涉及多种基因和信号转导途径，但遗传肿瘤标志物在肾癌诊断和预后预测中的应用还不多见。新的分子参数的确定和评估在癌症研究和癌症治疗中具有极其重要的意义。在此，我们提出了一种新的方法来快速识别肿瘤中临床相关的分子变化，以确定与肾癌相关的基因。首先对5184个克隆进行了cDNA阵列分析，以筛选肾癌细胞系CRL-1933与正常肾组织之间差异表达的基因。在癌细胞系中有89个差异表达基因，其中一个编码波形蛋白，一种细胞质中间丝。免疫组织化学方法检测Vimentin在肾透明细胞癌(51%)和乳头状肾癌(61%)中的表达，而在嫌色肾细胞癌(4%)和嗜酸细胞瘤(12%)中很少表达。此外，波形蛋白的表达与患者预后不良显著相关(P<；0.007)，与肿瘤的分级和分期无关。这些从微小排列的肿瘤样本中获得的结果与先前关于肾肿瘤中波形蛋白表达的发现很好地吻合。结论：肿瘤阵列和基因芯片相结合是快速鉴定和进一步评价在肿瘤生物学中起作用的基因的有效方法。
Many genes and signaling pathways are involved in renal cell carcinoma (RCC) development, However, genetic tumor markers have not gained use in RCC diagnostics and prognosis prediction. Identification and evaluation of new molecular parameters are of utmost importance in cancer research and cancer treatment. Here we present a novel approach to rapidly identify clinically relevant molecular changes in cancer, To identify genes with relevance to RCC, a cDNA array analysis was first performed on 5184 cDNA clones on a filter to screen for genes with differential expression between the renal cancer cell line CRL-1933 and normal kidney tissue. There were 89 differentially expressed genes in the cancer cell line, one of them coding for vimentin, a cytoplasmic intermediate filament. In a second step, a renal cancer tissue microarray containing 532 RCC specimen was used to determine vimentin expression by immunohistochemistry, Vimentin expression was seen frequently in clear cell (51%) and papillary RCC (61%), but rarely in chromophobe RCC (4%) and oncocytomas (12%). Furthermore, vimentin expression was significantly associated with poor patient prognosis (P < 0.007) independent of grade and stage. These results obtained from minute arrayed tumor samples match well with previous findings on vimentin expression in renal tumors. It is concluded that the combination of tumor arrays and cDNA arrays is a powerful approach to rapidly identify and further evaluate genes that play a role in tumor biology.