Axelsen Jacob Bock, Lotem Joseph, Sachs Leo, Domany Eytan
Department of Physics of Complex Systems, The Weizmann Institute of Science, Rehovot 76100, Israel.
Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13122-7. doi: 10.1073/pnas.0705824104. Epub 2007 Jul 30.
We have analyzed gene expression in different normal human tissues and different types of solid cancers derived from these tissues. The cancers analyzed include brain (astrocytoma and glioblastoma), breast, colon, endometrium, kidney, liver, lung, ovary, prostate, skin, and thyroid cancers. Comparing gene expression in each normal tissue to 12 other normal tissues, we identified 4,917 tissue-selective genes that were selectively expressed in different normal tissues. We also identified 2,929 genes that are overexpressed at least 4-fold in the cancers compared with the normal tissue from which these cancers were derived. The overlap between these two gene groups identified 1,340 tissue-selective genes that are overexpressed in cancers. Different types of cancers, including different brain cancers arising from the same lineage, showed differences in the tissue-selective genes they overexpressed. Melanomas overexpressed the highest number of brain-selective genes and this may contribute to melanoma metastasis to the brain. Of all of the genes with tissue-selective expression, those selectively expressed in testis showed the highest frequency of genes that are overexpressed in at least two types of cancer. However, colon and prostate cancers did not overexpress any testis-selective gene. Nearly all of the genes with tissue-selective expression that are overexpressed in cancers showed selective expression in tissues different from the cancers' tissue of origin. Cancers aberrantly expressing such genes may acquire phenotypic alterations that contribute to cancer cell viability, growth, and metastasis.
我们分析了不同正常人体组织以及源自这些组织的不同类型实体癌中的基因表达情况。所分析的癌症包括脑癌(星形细胞瘤和胶质母细胞瘤)、乳腺癌、结肠癌、子宫内膜癌、肾癌、肝癌、肺癌、卵巢癌、前列腺癌、皮肤癌和甲状腺癌。通过将每个正常组织中的基因表达与其他12种正常组织进行比较,我们鉴定出了4917个在不同正常组织中选择性表达的组织选择性基因。我们还鉴定出2929个基因,这些基因在癌症中的表达水平相比于其来源的正常组织至少高4倍。这两组基因的重叠部分鉴定出了1340个在癌症中过表达的组织选择性基因。不同类型的癌症,包括源自同一谱系的不同脑癌,在它们过表达的组织选择性基因上表现出差异。黑色素瘤过表达的脑选择性基因数量最多,这可能导致黑色素瘤转移至脑部。在所有具有组织选择性表达的基因中,那些在睾丸中选择性表达的基因在至少两种类型癌症中过表达的频率最高。然而,结肠癌和前列腺癌并未过表达任何睾丸选择性基因。几乎所有在癌症中过表达的具有组织选择性表达的基因在与癌症起源组织不同的组织中表现出选择性表达。异常表达此类基因的癌症可能会获得有助于癌细胞存活、生长和转移的表型改变。