Searching for pathogenic gene functions to cervical cancer

Searching for pathogenic gene functions to cervical cancer
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DOI:
10.1016/j.ygyno.2003.11.031
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发表时间:
2004-04-01
影响因子:
4.7
通讯作者:
Kim, YW
Kim, YW
中科院分区:
医学2区
文献类型:
--
作者:
Ahn, WS;Bae, SM;Kim, YW

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目标。与人乳头瘤病毒(HPV)感染相关的宫颈癌的分子病理学目前尚不清楚。为了澄清这一问题,我们研究了宫颈癌病变的基因表达谱和致病细胞过程。采用4700个基因的cDNA芯片、分层聚类和基因本体(GO)技术对11例浸润性癌(lb - IIIa期)患者的组织进行了研究。我们鉴定出74个基因,在11名患者中至少有8名患者的表达差异超过2倍。其中上调基因33个,下调基因41个。基因表达谱被分类为相互依赖的345个功能集,根据GO产生611个细胞过程。GO分析显示,宫颈癌发生过程中细胞死亡、蛋白质生物合成和核酸代谢完全下调。核酸结合基因和结构分子活性基因显著下调。相反,在骨骼发育、免疫反应和细胞外活动中,显著上调。这些数据表明,这些调控基因和细胞过程可以进一步用于宫颈癌患者的预后和诊断预测,并需要进一步研究和功能表征所鉴定的基因。(C) 2004爱思唯尔公司版权所有。
Objective. Molecular pathology of cervical cancers associated with human papillomavirus (HPV) infection is presently unclear. In an effort to clarify this issue, we investigated gene expression profiles and pathogenic cellular processes of cervical cancer lesions.Methods. Tissues of 11 patients (invasive cancer stages lb - IIIa) were investigated by a cDNA microarray of 4700 genes, hierarchical clustering and the Gene Ontology (GO).Results. We identified 74 genes showing a more than 2-fold difference in their expression in at least 8 out of 11 patients. Among these, 33 genes were up-regulated, in contrast, 41 genes were down-regulated. The gene expression profiles were classified into mutually dependent 345 function sets, resulting in 611 cellular processes according to the GO. The GO analysis showed that cervical carcinogenesis underwent complete down-regulation of cell death, protein biosynthesis, and nucleic acid metabolism. Also, genes belonging to nucleic acid binding and structural molecule activity were significantly down-regulated. In contrast, significant up-regulation was shown in skeletal development, immune response, and extracellular activity.Conclusion. These data suggest that the regulated genes and cellular processes could be further used for predicting prognosis and diagnosis of cervical cancer patients, and further investigation and functional characterization of the identified genes is warranted. (C) 2004 Elsevier Inc. All rights reserved.