表达谱基因芯片筛选结直肠癌转移中Tiam1相关基因

摘要

Purpose To screen and identify T cell lymphoma invasion and metastasis 1 (Tiam1) related genes and expression profile during distant metastasis of colorectal cancer. Methods Colorectal cancer( CRC) in a mice model was established by intraperitoneal injection of dimethylhydrazine ( DMH) . Five panels of fresh primary tumor tissues from Tiam1 transgenic mice were collected and com-pared with that from wild type mice. Differentially expressed genes were detected by Affymetrix human genome-wide expression profile chip and verified by real-time quantitative PCR ( qRT-PCR) analysis. Results The genechip result showed that 794 genes were differ-entially expressed by at least 3 folds in Tiam1 transgenic mice with distant metastasis of colorectal cancer tissue, including 400 up-regu-lated and 394 down-regulated ones. Bioinformatics analysis and gene co-expression network building identified 3 genes (PIK3R5, FIGF and RPS6KA6) with specific expression in colorectal cancer tissue with distant metastasis, and this result was confirmed by qRT-PCR. Conclusion A specific Tiam1 gene expression profile related to colorectal cancer distant metastasis has been established through screening and identifying the genes related to Tiam1 by gene chip technique. These findings provide a basis for exploring the molecular markers of colorectal cancer with distant metastasis.%目的：筛选在结直肠癌远处转移中T细胞淋巴瘤侵袭转移1(T-cell lymphoma invasion and metastasis 1, Tiam1)相关基因并鉴定其表达。方法腹腔注射二甲基肼( dimethylhydrazine, DMH)建立小鼠结直肠癌模型,收集Tiam1转基因小鼠和野生型小鼠的结直肠癌原发灶新鲜组织5对,应用Affymetrix小鼠全基因组表达谱芯片检测两组的差异表达基因,qRT-PCR技术验证部分差异基因以确定结果的可靠性。结果基因芯片检测结果显示差异在3倍以上的基因共794个,有远处转移的Ti-am1转基因小鼠结直肠癌组织中表达上调的基因共400个,下调基因共394个；通过生物信息学分析及GENEMANIA共表达网络构建,筛选3个(PIK3R5、FIGF、RPS6KA6)特异相关的差异基因进行qRT-PCR技术验证,验证结果与基因芯片结果检测相符。结论通过基因芯片技术筛选和鉴定结直肠癌转移中Tiam1相关基因,建立了特异性结直肠癌转移表达谱,为寻找结直肠癌远处转移的分子标志物提供依据。