Staub Eike, Groene Joern, Heinze Maya, Mennerich Detlev, Roepcke Stefan, Klaman Irina, Hinzmann Bernd, Castanos-Velez Esmeralda, Pilarsky Christian, Mann Benno, Brümmendorf Thomas, Weber Birgit, Buhr Heinz-Johannes, Rosenthal André
Max Planck Institute for Molecular Genetics, Department of Computational Molecular Biology, Berlin, Germany.
Mol Cancer. 2007 Dec 14;6:79. doi: 10.1186/1476-4598-6-79.
Colorectal tumors have characteristic genome-wide expression patterns that allow their distinction from normal colon epithelia and facilitate clinical prognosis. The expression heterogeneity within a primary colorectal tumor has not been studied on a genome scale yet. Here we investigated three compartments of colorectal tumors, the invasion front, the inner tumor mass, and surrounding normal epithelial tissue by microdissection and microarray-based expression profiling. In both tumor compartments many genes were differentially expressed when compared to normal epithelium. The sets of significantly deregulated genes in both compartments overlapped to a large extent and revealed various interesting known and novel pathways that could have contributed to tumorigenesis. Cells from the invasion front and inner tumor mass, however, did not show significant differences in their expression profile, neither on the single gene level nor on the pathway level. Instead, gene expression differences between individuals are more pronounced as all patient-matched tumor samples clustered in close proximity to each other. With respect to invasion front and inner tumor mass we conclude that the specific tumor cell micro-environment does not have a strong influence on expression patterns: largely similar genome-wide expression programs operate in the invasion front and interior compartment of a colorectal tumor.
结直肠肿瘤具有特征性的全基因组表达模式,这使其能够与正常结肠上皮区分开来,并有助于临床预后评估。原发性结直肠肿瘤内的表达异质性尚未在全基因组规模上进行研究。在此,我们通过显微切割和基于微阵列的表达谱分析,研究了结直肠肿瘤的三个部分:侵袭前沿、肿瘤内部肿块以及周围正常上皮组织。与正常上皮相比,在两个肿瘤部分中许多基因的表达存在差异。两个部分中显著失调的基因集在很大程度上重叠,并揭示了各种可能促成肿瘤发生的有趣的已知和新途径。然而,侵袭前沿和肿瘤内部肿块的细胞在表达谱上无论是在单个基因水平还是在通路水平上都没有显示出显著差异。相反,个体之间的基因表达差异更为明显,因为所有患者匹配的肿瘤样本彼此紧密聚集。关于侵袭前沿和肿瘤内部肿块,我们得出结论,特定的肿瘤细胞微环境对表达模式没有强烈影响:在结直肠肿瘤的侵袭前沿和内部区域运行着大致相似的全基因组表达程序。