A molecular signature of metastasis in primary solid tumors
A molecular signature of metastasis in primary solid tumors
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DOI：
10.1038/ng1060
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发表时间：
2003-01-01
期刊：
影响因子：
30.8
通讯作者：
Golub, TR
中科院分区：
文献类型：
--
作者：
Ramaswamy, S;Ross, KN;Golub, TR
转移是导致癌症患者死亡的主要事件，但人们对其分子基础知之甚少。为了探索人类原发肿瘤和转移癌之间的分子差异，我们比较了多种肿瘤类型的腺癌转移和不匹配的原发腺癌的基因表达谱。我们发现了区分原发腺癌和转移性腺癌的基因表达特征。更值得注意的是，我们发现，就这种基因表达特征而言，原发肿瘤的一部分类似于转移性肿瘤。我们通过将表达签名应用于279个不同类型的原发实体肿瘤的数据来证实这一发现。我们发现携带基因表达特征的实体瘤最有可能与转移和不良的临床结果相关(P<；0.03)。这些结果表明，人类肿瘤的转移潜力编码在原发肿瘤的大部分中，从而挑战了转移来自原发肿瘤内具有转移能力的稀有细胞的观点。
Metastasis is the principal event leading to death in individuals with cancer, yet its molecular basis is poorly understood(1). To explore the molecular differences between human primary tumors and metastases, we compared the gene-expression profiles of adenocarcinoma metastases of multiple tumor types to unmatched primary adenocarcinomas. We found a gene-expression signature that distinguished primary from metastatic adenocarcinomas. More notably, we found that a subset of primary tumors resembled metastatic tumors with respect to this gene-expression signature. We confirmed this finding by applying the expression signature to data on 279 primary solid tumors of diverse types. We found that solid tumors carrying the gene-expression signature were most likely to be associated with metastasis and poor clinical outcome (P < 0.03). These results suggest that the metastatic potential of human tumors is encoded in the bulk of a primary tumor, thus challenging the notion that metastases arise from rare cells within a primary tumor that have the ability to metastasize(2).