人肺腺癌与癌旁组织mRNA差异表达及信号通路的变化

Changes of mRNAs Expression Profiling and Signaling Pathways Between Human Pulmonary Adenocarcinoma and Paraneoplastic Tissues

目的:利用全基因组表达谱芯片对人肺腺癌和癌旁组织中差异表达的mRNA进行检测,对mRNA在肺腺癌发生过程中可能涉及到的信号通路变化进行分析。方法:提取6例人肺腺癌与癌旁组织标本中的总RNA,体外逆转录制备ds-cDNA并用Cy3荧光标记,与含有19 000条mRNA的芯片进行杂交,扫描软件扫描芯片荧光信号图像,筛选差异表达的mRNA并进行信号通路分析。结果:1差异表达的mRNA总共有832条,其中在肿瘤组织中相对高表达的mRNA有407条,相对低表达的mRNA有425条(大于2倍变化且P<0.05)。2信号通路分析发现差异表达的mRNA参与了9个信号通路的调控,其中同源重组信号通路、人转化生长因子-β通路、丝裂原激活蛋白激酶信号通路、细胞周期信号通路、p53信号通路等5条信号通路与肿瘤的发生有关。结论:人肺腺癌组织中有大量mRNA发生差异表达,差异表达的mRNA在多个与肺腺癌发生密切相关的信号通路中发挥重要的调控作用。

Objective. To detect the difference of mRNA expression profiling between human pulmonary adenocarcinoma and paraneoplastic tissues and identify the changes in signaling pathways by whole genome expression microarray screening. Methods： Six samples of total RNA from human pulmonary adenocarcinoma and paraneoplastic tissues were extracted, mRNA was reversely tran- scripted into ds-cDNA in vitro and fluorescently labeled with Cy3 then hybridized with chips con- taining 19 000 mRNAs. The chip fluorescence signal image was scanned to determine the differ- ential expression of mRNAs and the changes in signaling pathways. Results： ①Among the 19 000 mRNAs, 832 were differentially expressed in pulmonary adenocarcinoma tissues, in which 407 mRNAs were up-regulated and 425 mRNAs were down-regulated compared with the paraneoplas- tie tissues （2 fold changes and P〈0.05）. ②Nine signaling pathways were involved based on mR- NAs expression data and 5 of which were involved in tumorigenesis （homologous recombination,TGF-β signaling pathway, MAPK signaling pathway, cell cycle and p53 signaling pathway）. Conclusion： ①Obvious changes of mRNAs expression profiling were observed in the human pul- monary adenocarcinoma. ②Differentially expressed mRNAs play an important role in regulating signaling pathways in the human pulmonary adenocarcinoma tumorgenesis.