利用生物信息学研究 Tgfβ信号通路在人类结直肠癌发生发展中的作用

摘要

目的：：系统性研究经典Tgfβ信号通路各成员,在人类早期结直肠癌组织中,转录水平上的表达差异,以探索Tgfβ信号通路在人类结直肠癌发生中作用机制。方法：利用生物信息学手段,在GEO数据库中下载符合纳入标准的早期人类结直肠癌芯片结果,通过UltralEdit软件实现探针号和基因名的转换以建立全转录本表达数据表；通过KEGG信号通路图谱选择Tgfβ信号经典通路待测分子,统计学分析各待测分子在正常组癌症组中的表达差异。结果：在GEO数据库中下载和获得符合纳入标准的早期人类结直肠癌结直肠癌芯片12组基因芯片结果,对Tgfβ信号通路及其旁路共27个进行表达差异分析,其中表达水平上调的分子4个,下调的基因3个,具有或接近显著性意义。结论：在直肠癌发生过程中,Smads分子的表达下降阻断经典的Tgfβ信号的抗肿瘤作用,同时配体分子和受体分子的广泛上调可能刺激旁路分子的激活从而导致肿瘤的发生。%Objective: Systematic study of the transcriptional expression levels of canonical Tgfβ signaling pathways in early human colorectal cancer tissues, to shed light on molecular mechanism of canonical Tgfβ signaling underling the onset of human colorectal cancer. Methods: Using bioinformatic analysis, twelve sets of gene chip data that meet the criteria were downloaded from GEO database. By using UltraEdit software to convert the gene and probes name,to estab-lish gene expression corresponding names and sample data tables;using the KEGG pathway maps to inquiry the members of Tgfβsignaling pathway, using the Exel’ s TTEST function to calculate the sigifcance of each gene. Results:In the de-velopment process of the human colorectal cancer, there are twenty-seven genes involved in the Tgfβsignaling pathway of twelve sets of gene chip data, where 4 genes up-regulated and 3 down-regulated. Conclusion:During the colorectal tu-morigenesis, the decrease of Smads block the anti-cancer roles of canonical Tgfβ, and the increase of Tgfβ ligands and receptors induce the non-canonical pathway, which contribute to colorectal cancer progress.