Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray
Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray
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DOI：
10.1111/j.1349-7006.2003.tb01446.x
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发表时间：
2003-04-01
期刊：
影响因子：
5.7
通讯作者：
Okabe, H
中科院分区：
文献类型：
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作者：
Suganuma, K;Kubota, T;Okabe, H
本研究利用基因芯片技术筛选胃癌化疗耐药相关基因。应用寡核苷酸芯片技术对1998 ~ 1999年在我所手术切除的35例胃癌标本进行了6300个基因表达的定量研究，并与MTT法（tetrazolium based 3（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide）测定的胃癌耐药率进行了比较。测定顺铂（DDP）、5-氟尿嘧啶（541，11）、丝裂霉素C或阿霉素的抑制率（IR）。IR ≥ 60%为敏感，IR ≤ 40%为耐药。成功完成了DDP的聚类，从而选择了23个候选基因作为DDP耐药相关基因，包括血管通透性因子、2个膜转运亚基和视网膜母细胞瘤结合蛋白-1。此外，根据以下标准进一步筛选DDP耐药相关基因：1）在70%以上的耐药肿瘤中可以检测到该基因的表达。2)在不到30%的敏感肿瘤中可以检测到表达。3)在超过50%的标本中，肿瘤中的表达是正常粘膜的两倍以上。金属硫蛋白-IG和肝素结合表皮生长因子样生长因子（HB-EGF）被确定为候选的DDP耐药相关基因。当根据MTT试验结果分析已知的DDP抗性相关基因时，谷胱甘肽-S-转移酶和环氧合酶-2基因家族也被评估为抗性相关基因。对于5-FU耐药，二氢嘧啶脱氢酶和HB-EGF样生长因子基因也被认为是耐药相关基因。目前的研究表明，寡核苷酸芯片可以提供有关癌症的耐药因子的信息。
To identify chemo resistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium-based 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (541,11), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP-resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, further selection of DDP-resistance-related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidate DDP-resistance-related genes. When known DDP-resistance-related genes were analyzed according to the MTT assay result, families of glutathione-S-transferase and cyclooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, dihydropyrimidine dehydrogenase and HB-EGF-like growth factor genes were also suggested to be resistance-related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer.