Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles
Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles
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DOI：
10.1016/s0002-9440(10)62509-6
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发表时间：
2001-10-01
影响因子：
6
通讯作者：
Hanash, S
中科院分区：
文献类型：
--
作者：
Giordano, TJ;Shedden, KA;Hanash, S
基于基因表达谱的肿瘤分子分类有望显著改善癌症患者的诊断和管理。器官特异性基因表达模式的建立是分子方法临床应用的关键第一步。在这里，我们报告了154例原发性肺、结肠和卵巢腺癌的基因表达谱。使用高密度寡核苷酸阵列与7129个基因探针集，57个肺，51个结肠，和46个卵巢腺癌的综合基因表达谱，并进行主成分分析和交叉验证的预测分析，使用最近邻分类。这些统计分析导致154个腺癌中的152个以器官特异性方式分类，并鉴定了每种肿瘤类型以假定的组织特异性方式表达的基因。此外，确定了两个肿瘤，一个在结肠组，另一个在卵巢组，不符合各自的器官特异性队列。通过免疫组织化学分析对这些异常肿瘤进行研究，发现卵巢肿瘤与结肠来源的转移性腺癌一致，结肠肿瘤是多形性间叶细胞。肿瘤，可能是平滑肌肉瘤，而不是上皮肿瘤。我们的结果证明了基因表达谱对肿瘤分类的能力，并提示器官特异性基因表达谱的测定将在包括分子诊断和分类在内的多种临床环境中发挥重要作用。
Molecular classification of tumors based on their gene expression profiles promises to significantly refine diagnosis and management of cancer patients. The establishment of organ-specific gene expression patterns represents a crucial first step in the clinical application of the molecular approach. Here, we report on the gene expression profiles of 154 primary adenocarcinomas of the lung, colon, and ovary. Using high-density oligonucleotide arrays with 7129 gene probe sets, comprehensive gene expression profiles of 57 lung, 51 colon, and 46 ovary adenocarcinomas were generated and subjected to principle component analysis and to a cross-validated prediction analysis using nearest neighbor classification. These statistical analyses resulted in the classification of 152 of 154 of the adenocarcinomas in an organ-specific manner and identified genes expressed in a putative tissue-specific manner for each tumor type. Furthermore, two tumors were identified, one in the colon group and another in the ovarian group, that did not conform to their respective organ-specific cohorts. Investigation of these outlier tumors by immunohistochemical profiling revealed the ovarian tumor was consistent with a metastatic adenocarcinoma of colonic origin and the colonic tumor was a pleomorphic mesenchymal. tumor, probably a leiomyosarcoma, rather than an epithelial tumor. our results demonstrate the ability of gene expression profiles to classify tumors and suggest that determination of organ-specific gene expression profiles will play a significant role in a wide variety of clinical settings, including molecular diagnosis and classification.