Identification of genes whose expression is associated with cisplatin resistance in human ovarian carcinoma cells
Identification of genes whose expression is associated with cisplatin resistance in human ovarian carcinoma cells
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DOI：
10.1007/s00280-005-0171-8
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发表时间：
2006-09-01
影响因子：
3
通讯作者：
Howell, Stephen B.
中科院分区：
文献类型：
--
作者：
Cheng, Timothy C.;Manorek, Gerald;Howell, Stephen B.
本研究的目的是确定基因一致差异表达的多对等基因顺铂（DDP）敏感和耐药的人卵巢癌细胞系，使用基于微阵列的表达谱。在相同条件下生长的六对卵巢癌细胞系上进行表达谱分析;每个细胞表达谱独立地重复六次。没有基因在所有六对细胞中差异表达，甚至在六对细胞中的任何五对中也没有差异表达。在至少4个细胞对中，18个基因和1个EST上调，4个基因和1个EST下调。其中，只有金属硫蛋白2A先前与DDP耐药性有关。在基于六次重复鉴定的基因中，如果仅进行五次重复，则平均24.8%会被遗漏，并且如果仅进行四次重复，则38.3%会被遗漏。基因没有确定一个显性的生化途径或本体分类与DDP耐药;然而，分层聚类提供了两类DDP耐药表型的证据，其中有额外的细胞对特异性改变。本研究中发现的许多基因在细胞表面相互作用和转运途径中发挥重要作用，这些基因以前与DDP耐药性无关。通过这种广泛重复的分析发现的基因是预测卵巢癌患者DDP反应性的候选基因。
The goal of this study was to identify genes consistently differentially expressed in multiple pairs of isogenic cisplatin (DDP)-sensitive and resistant human ovarian carcinoma cell lines using microarray-based expression profiling. Expression profiling was carried out on six pairs of ovarian carcinoma cells lines growing under identical conditions; each cell expression profile was independently replicated six times. No genes were differentially expressed in all six pairs of cells or even in even in any five of the six pairs. Eighteen genes and 1 EST were upregulated, and four genes and 1 EST were downregulated, in at least four cell pairs. Of these, only metallothionein 2A has previously been implicated in DDP resistance. Among the genes identified on the basis of six replicates, an average of 24.8% would have been missed if only five replicates had been performed, and 38.3% would have been missed with only four replicates. The genes did not identify a dominant biochemical pathway or ontology category as being linked to DDP resistance; however, hierarchical clustering provided evidence for two classes DDP-resistant phenotypes within which there are additional cell pair-specific alterations. Many of the genes identified in this study play important roles in cell surface interactions and trafficking pathways not previously linked to DDP resistance. The genes discovered by this extensively replicated analysis are candidates for prediction of DDP responsiveness in ovarian cancer patients.