利用cDNA微阵列研究胃肠间质瘤耐药、复发相关基因的表达

Analysis of recurrence-associated and imatinib resistance-associated gene expression in gastrointestinal stromal tumor by cDNA microarray

目的 观察复发与未复发胃肠间质瘤（GIST）间的基因表达差异,探讨恶性GIST伊马替尼耐药、复发发生发展机制.方法 收集5对患者的新鲜复发及未复发GIST组织随机配对成组行cDNA微阵列研究.应用荧光定量聚合酶链反应（PCR）方法对芯片结果进行验证.结果 复发与未复发GIST间的差异表达基因共1088个,其中表达上调者592个,下调者496个;上调基因功能主要与信号传导、肿瘤发生、药物代谢、细胞黏附等相关;下调基因功能则主要与细胞间隙连接通讯、肿瘤抑制、补体免疫防御等相关;GIST相关基因c-kit（CD117）、CD34在两组间差异均无统计学意义;荧光定量PCR验证结果与芯片表达结果一致.结论 运用cDNA芯片进行基因表达谱分析,有助于探讨GIST复发、伊马替尼耐药机制并寻找新的治疗靶标.

Objective To study the differential expression of recurrence-associated and imatinib resistance-associated gene between recurrent and unrecurrent gastrointestinal stromal tumors （GIST） and explore the molecular mechanism of drug resistance and recurrence of malignant GIST by cDNA microarray analysis.Methods A total of 5 pairs of recurrent and unrecurrent fresh GIST tissues were subjected to cDNA microarray with 41000 genes.Array results were validated by reverse transcription-polymerase chain reaction （RT-PCR）.Results There were 1088 differential expression genes between recurrent and unrecurrent GIST tissues,including 592 genes up-regulated and 496 down-regulated.Most of the overexpressed genes were related to signaling pathway,oncogenesis,drug metabolism,cell adhesion,and the down-regulated genes were related to gap junction,tumor suppression,complement imumune defense.GIST related genes （c-kit,CD34） had no significant difference between recurrent and unrecurrent GIST tissues.RT-PCR confirmed the aAbstract：Objective To study the differential expression of recurrence-associated and imatinib resistance-associated gene between recurrent and unrecurrent gastrointestinal stromal tumors （GIST） and explore the molecular mechanism of drug resistance and recurrence of malignant GIST by cDNA microarray analysis.Methods A total of 5 pairs of recurrent and unrecurrent fresh GIST tissues were subjected to cDNA microarray with 41000 genes.Array results were validated by reverse transcription-polymerase chain reaction （RT-PCR）.Results There were 1088 differential expression genes between recurrent and unrecurrent GIST tissues,including 592 genes up-regulated and 496 down-regulated.Most of the overexpressed genes were related to signaling pathway,oncogenesis,drug metabolism,cell adhesion,and the down-regulated genes were related to gap junction,tumor suppression,complement imumune defense.GIST related genes （c-kit,CD34） had no significant difference between recurrent and unrecurrent GIST tissues.RT-PCR confirmed the array results.Conclusion Gene expression profiling by cDNA microarray analysis provides not only molecular understanding of recurrence mechanism and imatinib resistance mechanism of GIST,but may also be helpful in discovering new therapeutic targets for recurrent and imatinib resistant GIST.