Gene expression analysis for predicting gemcitabine sensitivity in pancreatic cancer patients.
Gene expression analysis for predicting gemcitabine sensitivity in pancreatic cancer patients.
复制标题
DOI：
10.1080/13651820601175918
复制
发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Nagai, Hideo
中科院分区：
文献类型：
--
作者：
Bai, Jianfeng;Sata, Naohiro;Nagai, Hideo
背景/目的：目前的体外药敏试验存在局限性和不足。本研究利用基因表达数据预测胰腺癌对吉西他滨的敏感性。材料和方法：采用胶原滴药敏试验(CD-DST)检测14例胰腺癌患者癌细胞对吉西他滨的体外敏感性。根据这项测试，14种癌症中有9种被确认为吉西他滨敏感或耐药。从这9种肿瘤中提取总RNA，并以此为模板合成Cy3标记的cDNA。以6例正常人的胰腺RNA为对照。标记的探针与Atlas Glass Human 1.0微阵列芯片杂交，然后对芯片进行清洗和扫描，并使用Microsoft Excel嵌入式软件对数据进行分析。结果：芯片数据统计分析表明，在吉西他滨敏感的肿瘤中有4个基因存在差异表达：微粒体谷胱甘肽S转移酶1(GSTT1)、拓扑异构酶IIα(TOP2A)、半胱氨酸天冬氨酸氨基转移酶3(Caspase3)、三磷酸腺苷结合盒和C亚家族成员2(ABCC2)。另外还有20多个基因被鉴定为可能与耐药相关的候选基因。结论：耐药相关基因的表达似乎可以预测癌症是吉西他滨敏感还是耐药。进一步的研究将使建立基于基因表达的耐药性评分系统成为可能。这样的系统将允许更有效地应用化疗。
BACKGROUND/AIMS: Current in vitro drug sensitivity tests have limitations and disadvantages. This study investigated the use of gene expression data to predict the sensitivity of pancreatic cancers to gemcitabine.MATERIALS AND METHODS: Cancer cells isolated from 14 pancreatic cancer patients were tested in vitro for gemcitabine sensitivity using the collagen droplet drug sensitivity test (CD-DST). On the basis of this test, 9 of the 14 cancers were identified as either gemcitabine-sensitive or gemcitabine-resistant. Total RNA was extracted from each of those nine cancers and used as a template to synthesize Cy3-labeled cDNA. Pancreatic RNA extracted from six normal individuals was used as a control. Labeled probes were hybridized to an Atlas Glass Human 1.0 Microarray chip, after which the chips were washed and scanned, and the data were analyzed using Microsoft Excel-embedded software. The expression profiles of selected genes were confirmed using real-time PCR analysis.RESULTS: Statistical analysis of the microarray data showed that four genes were differentially expressed in gemcitabine-sensitive cancers: microsomal glutathione S-transferase 1 (GSTT1), topoisomerase II alpha (TOP2A), caspase 3, and ATP-binding cassette and subfamily C member 2 (ABCC2). More than 20 other genes were additionally identified as possible candidate genes associated with drug resistance.CONCLUSIONS: Expression of drug resistance-related genes appeared to predict whether a cancer was gemcitabine-sensitive or -resistant. Further study will enable a drug resistance scoring system to be established on the basis of gene expression. Such a system will allow more efficient application of chemotherapy.