The gene expression profile represents the molecular nature of liver metastasis in colorectal cancer.
The gene expression profile represents the molecular nature of liver metastasis in colorectal cancer.
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DOI：
10.3892/ijo.30.1.129
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发表时间：
2007
影响因子：
5.2
通讯作者：
M. Yamasaki;I. Takemasa;T. Komori;S. Watanabe;M. Sekimoto;Y. Doki;K. Matsubara;M. Monden
中科院分区：
文献类型：
--
作者：
M. Yamasaki;I. Takemasa;T. Komori;S. Watanabe;M. Sekimoto;Y. Doki;K. Matsubara;M. Monden
结直肠癌的主要死亡原因与肝转移有关。虽然转移过程已经得到了很好的研究，转移的分子遗传学基础的许多方面仍然不清楚。阐明肝转移的分子本质是改善结直肠癌预后的当务之急。我们分析了104个结直肠癌样本的时间顺序基因表达谱对应的致癌发展，包括正常粘膜，局部和转移的原发性肿瘤，肝转移病灶的基本样本，使用自定义的cDNA微阵列。将104例肿瘤组织中的基因表达谱分为4组，每组基因表达谱均能反映肿瘤的转移过程。为了研究原发性肿瘤中转移潜能的存在，使用通过时间分析检测的转移相关基因，我们对28个独立的原发性肿瘤进行了分层聚类和监督分类分析。分层聚类分析根据肿瘤的最终转移状态而不是其临床分期将肿瘤分离，并且转移的原发性肿瘤的概况类似于除了原发性病变之外的转移性病变而不是非转移的原发性肿瘤。使用监督分类方法，这些基因的表达谱允许将诊断为局部癌症的肿瘤根据其最终转移状态分为两类，局部和转移类。局限性组的无病生存期和总生存期明显长于转移性组。基因表达谱的时序分析提供了对转移过程的更好理解。我们的研究结果表明，转移潜能已经在原发性肿瘤中编码，并且可以通过基因表达谱检测，这允许预测诊断为局部肿瘤的患者的肝转移，并且还可以设计用于治疗和诊断结直肠癌的新策略。
The major cause of death in colorectal cancer is related to liver metastasis. Although the metastatic process has been well studied, many aspects of the molecular genetic basis of metastasis remain unclear. Elucidation of the molecular nature of liver metastasis is urgent to improve the outcome of colorectal cancer. We analyzed the chronological gene expression profiles of 104 colorectal samples corresponding to oncogenic development including normal mucosa, localized and metastasized primary tumors, and liver metastatic lesions as fundamental samples using a custom cDNA microarray. The gene expression patterns in 104 samples were classified into four groups closely associated with their metastatic status, and the genes of each group appropriately reflected the metastatic process. To investigate the existence of metastatic potential in primary tumors using metastasis-related genes detected by chronological analysis, we performed a hierarchical cluster and supervised classification analysis of 28 independent primary tumors. Hierarchical cluster analysis segregated the tumors according to their final metastatic status, rather than their clinical stages, and the profile of metastasized primary tumors resembled one of a metastatic lesion apart from a primary lesion rather than one of a non-metastasized primary tumor. Using the supervised classification approach, the expression profile of these genes allowed the classification of tumors diagnosed as localized cancer into two classes, the localized and the metastasized class, according to their final metastatic status. The disease-free survival and overall survival were significantly longer in the localized class than the metastasized class. Chronological analysis of the gene expression profile provides a better understanding of the metastatic process. Our results suggest that the metastatic potential is already encoded in the primary tumor and is detectable by a gene expression profile, which allows the prediction of liver metastasis in patients diagnosed with localized tumors and also the design of new strategies for the treatment and diagnosis of colorectal cancer.