Stage-specific alterations of the genorne, transcriptorne, and proteome during colorectal carcinogenesis
Stage-specific alterations of the genorne, transcriptorne, and proteome during colorectal carcinogenesis
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DOI：
10.1002/gcc.20382
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发表时间：
2007-01-01
影响因子：
3.7
通讯作者：
Ried, Thomas
中科院分区：
文献类型：
--
作者：
Habermann, Jens K.;Paulsen, Ulrike;Ried, Thomas
为了确定结直肠癌进展过程中基因组、转录组和蛋白质组的连续变化，我们分析了36名患者的组织样本，包括8名患者的完整粘膜-腺瘤-癌序列。比较基因组杂交（CGH）显示模式的阶段特异性，经常性的基因组不平衡。基因表达谱分析显示，正常粘膜与腺瘤之间差异表达基因58个，腺瘤与癌之间差异表达基因116个，原发癌与肝转移癌之间差异表达基因158个（P < 0.001）。通过双向凝胶电泳和随后的质谱分析蛋白质表达。虽然没有直接匹配的差异表达的蛋白质和基因，他们中的大多数属于相同的途径或网络。总之，增加的基因组不稳定性和染色体不平衡的复发模式以及特定的基因和蛋白质表达变化与结直肠癌进展的不同阶段相关。染色体非整倍性直接影响平均常驻基因表达水平，从而导致细胞转录组的大量失调。新基因和蛋白质的鉴定可能为诊断和治疗干预提供分子靶点。本文包含可在http：//www.example.com上获得的补充材料。www.interscience.wiley.com/jpages/1045-2257/suppmat (c)2006 Wiley-Liss，Inc.（匕首）
To identify sequential alterations of the genome, transcriptome, and proteome during colorectal cancer progression, we have analyzed tissue samples from 36 patients, including the complete mucosa-adenoma-carcinoma sequence from 8 patients. Comparative genomic hybridization (CGH) revealed patterns of stage specific, recurrent genomic imbalances. Gene expression analysis on 9K cDNA arrays identified 58 genes differentially expressed between normal mucosa and adenoma, 116 genes between adenoma and carcinoma, and 158 genes between primary carcinoma and liver metastasis (P < 0.001), Parallel analysis of our samples by CGH and expression profiling revealed a direct correlation of chromosomal copy number changes with chromosome-specific average gene expression levels. Protein expression was analyzed by two-dimensional gel electrophoresis and subsequent mass spectrometry. Although there was no direct match of differentially expressed proteins and genes, the majority of them belonged to identical pathways or networks. In conclusion, increasing genomic instability and a recurrent pattern of chromosomal imbalances as well as specific gene and protein expression changes correlate with distinct stages of colorectal cancer progression. Chromosomal aneuploidies directly affect average resident gene expression levels, thereby contributing to a massive deregulation of the cellular transcriptome. The identification of novel genes and proteins might deliver molecular targets for diagnostic and therapeutic interventions. This article contains Supplementary Material available at http:// www.interscience.wiley.com/jpages/1045-2257/suppmat. (c) 2006 Wiley-Liss, Inc.(dagger)