Gene expression profiling of clear cell renal cell carcinoma: Gene identification and prognostic classification
Gene expression profiling of clear cell renal cell carcinoma: Gene identification and prognostic classification
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DOI：
10.1073/pnas.171209998
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发表时间：
2001-08-14
影响因子：
11.1
通讯作者：
Teh, BT
中科院分区：
文献类型：
--
作者：
Takahashi, M;Rhodes, DR;Teh, BT
为了更好地了解肾透明细胞癌(CcRCC)发生和发展的分子机制，我们利用21,632个基因芯片研究了29例来自不同临床结局的ccRCC肿瘤的基因表达谱。我们确定了基因表达的改变，这些改变在大多数研究的肾细胞癌中都是常见的，在临床亚群中是独一无二的。相对非侵袭性疾病的患者[5年存活率为100%，大多数(15/17或88%)没有临床转移的证据]与相对侵袭性疾病的患者(平均生存期25.4个月，5年生存率为0%)之间的基因表达谱有显著差异。大约有40个基因最准确地做出了这种区分，其中一些基因以前被认为与转化和转移有关。为了测试这种分子差异的稳健性和潜在的临床实用性，我们模拟了它在临床环境中作为预后工具的使用。在接受检测的96%的ccRCC病例中，预测结果与临床结果一致，超过了分期预测的准确性。这些结果表明，ccRCC存在两种不同的分子形式，表达谱数据与临床参数的结合有助于提高ccRCC的诊断和预后。此外，识别的基因有助于深入了解侵袭性肾细胞癌的分子机制，并提出干预策略。
To better understand the molecular mechanisms that underlie the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC), we studied the gene expression profiles of 29 ccRCC tumors obtained from patients with diverse clinical outcomes by using 21,632 cDNA microarrays. We identified gene expression alterations that were both common to most of the ccRCC studied and unique to clinical subsets. There was a significant distinction in gene expression profile between patients with a relatively non-aggressive form of the disease [100% survival after 5 years with the majority (15/17 or 88%) having no clinical evidence of metastasis] versus patients with a relatively aggressive form of the disease (average survival time 25.4 months with a 0% 5-year survival rate). Approximately 40 genes most accurately make this distinction, some of which have previously been implicated in turnorigenesis and metastasis. To test the robustness and potential clinical usefulness of this molecular distinction, we simulated its use as a prognostic tool in the clinical setting. In 96% of the ccRCC cases tested, the prediction was compatible with the clinical outcome, exceeding the accuracy of prediction by staging. These results suggest that two molecularly distinct forms of ccRCC exist and that the integration of expression profile data with clinical parameters could serve to enhance the diagnosis and prognosis of ccRCC. Moreover, the identified genes provide insight into the molecular mechanisms of aggressive ccRCC and suggest intervention strategies.