Shen Huali, Zhong Fan, Zhang Yang, Yu Hongxiu, Liu Yinkun, Qin Lunxiu, He Fuchu, Tang Zhaoyou, Yang Pengyuan
Department of Systems Biology for Medicine and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, P. R. China.
Department of Chemistry, Fudan University, Shanghai, P. R. China.
Proteomics. 2015 Jun;15(11):1793-800. doi: 10.1002/pmic.201400275. Epub 2015 Mar 18.
Previously isolated pathways screened from individual genes were investigated at either the transcriptional or translational level; however, the consistency between the pathways screened at the gene expression levels was obscure in metastatic human hepatocellular carcinoma (HCC). To elucidate this question, we performed a transcriptomic (16,353 genes) and proteomic (7861 proteins) analysis simultaneously on six metastatic HCC cell lines against two nonmetastatic HCC cell lines, with all HBV traceable and close genetic-backgrounds for a comparative study. The quantitative and integrated results showed that significant genes were screened differentially with 351 transcripts from the transcriptome and 304 proteins from the proteome, with limited overlapping genes (7%). However, we discovered that these discrete 351 transcripts and 304 proteins screened share extrusive significant-pathways/networks with a 77% overlap, including active TGF-β, RAS, NFκB, and Wnt, and inactive HNF4A, which are responsible for HCC metastasis. We conclude that the discrete, but significant genes predicted by either ome play intrinsically important roles in the linkage of responsible pathways shared by both omes in HCC metastasis.
以往从单个基因筛选出的通路是在转录或翻译水平进行研究的；然而，在转移性人类肝细胞癌（HCC）中，基因表达水平筛选出的通路之间的一致性并不明确。为了阐明这个问题，我们对六种转移性肝癌细胞系和两种非转移性肝癌细胞系同时进行了转录组学（16353个基因）和蛋白质组学（7861种蛋白质）分析，所有样本乙肝病毒可溯源且遗传背景相近，用于比较研究。定量和综合结果表明，转录组中有351个转录本和蛋白质组中有304种蛋白质被差异筛选为显著基因，重叠基因有限（7%）。然而，我们发现筛选出的这351个离散转录本和304种蛋白质共享突出的显著通路/网络，重叠率为77%，包括活跃的转化生长因子-β（TGF-β）、RAS、核因子κB（NFκB）和Wnt，以及不活跃的肝细胞核因子4A（HNF4A），它们与肝癌转移有关。我们得出结论，转录组和蛋白质组预测的离散但显著的基因在肝癌转移中两个组学共享的相关通路联系中发挥着内在重要作用。
