Cancer Res Treat. 2003 Oct;35(5):451-9. doi: 10.4143/crt.2003.35.5.451.
The molecular pathology of cervical cancers associated with human papillomavirus infection is presently unclear. In an effort to clarify this issue, the gene expression profiles and pathogenic cellular processes of cervical cancer lesions were investigated.
Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, The Catholic University of Korea. The disease status was assigned according to the International Federation of Gynecology and Obstetrics. The tissue samples of 11 patients (invasive cancer stage Ib- IIIa) were investigated by a cDNA microarray of 4, 700 genes, hierarchical clustering and the Gene Ontology (GO). Total RNA from cervical cancer and non-lesional tissues were labeled with Cy5 and Cy3. The HaCaT human epithelial keratinocyte cell line was used as a negative control cell. The stages of invasive cancer were Ib to IIIb. All specimens were obtained by punch-biopsies and frozen in liquid nitrogen until required.
74 genes, showing more than a 2 fold difference in their expressions, were identified in at least 8 of the 11 patients. Of these genes, 33 were up-regulated and 41 were down-regulated. The gene expression profiles were classified into 345 mutually dependent function sets, resulting in 611 cellular processes according to their GO. The GO analysis showed that cervical carcinogenesis underwent complete down-regulation of cell death, protein biosynthesis and nucleic acid metabolism. The genes related to nucleic acid binding and structural molecule activity were also significantly down-regulated. In contrast, significant up-regulation was shown in the skeletal development, immune response and extracellular activity.
These data are suggestive of potentially significant pathogenetic cellular processes, and showed that the down-regulated functional profiling has an important impact on the discovery of pathogenic pathways in cervical carcinogenesis. GO analysis can also overcome the complexity of the expression profiles of the cDNA microarray via a cellular process level approach. Thereby, a valuable prognostic candidate gene, with real relevance to disease-specific pathogenesis, can be found at the cellular process levels.
与人类乳头瘤病毒感染相关的宫颈癌的分子病理学目前尚不清楚。为了阐明这一问题，我们研究了宫颈癌病变的基因表达谱和发病细胞过程。
从韩国天主教大学妇产科获得宫颈癌活检。根据国际妇产科联合会（FIGO）对疾病状况进行了分配。对 11 名患者（浸润性癌症 Ib-IIIa 期）的组织样本进行了 4700 个基因的 cDNA 微阵列、层次聚类和基因本体论（GO）分析。来自宫颈癌和非病变组织的总 RNA 用 Cy5 和 Cy3 标记。HaCaT 人上皮角质形成细胞系用作阴性对照细胞。浸润性癌分期为 Ib 至 IIIb。所有标本均通过打孔活检获得，并在液氮中冷冻直至需要。
在至少 8 名患者中，发现了 74 个表达差异超过 2 倍的基因。其中 33 个基因上调，41 个基因下调。根据其 GO，基因表达谱被分类为 345 个相互依赖的功能集，导致 611 个细胞过程。GO 分析表明，宫颈癌发生经历了细胞死亡、蛋白质生物合成和核酸代谢的完全下调。与核酸结合和结构分子活性相关的基因也明显下调。相比之下，在骨骼发育、免疫反应和细胞外活性方面显示出显著的上调。
这些数据提示了潜在的重要发病细胞过程，并表明下调的功能谱对宫颈癌发病机制中致病途径的发现具有重要影响。GO 分析还可以通过细胞过程水平的方法克服 cDNA 微阵列表达谱的复杂性。因此，可以在细胞过程水平找到具有真正疾病特异性发病机制相关性的有价值的预后候选基因。
