Lin H-M, Chatterjee A, Lin Y-H, Anjomshoaa A, Fukuzawa R, McCall J L, Reeve A E
Cancer Genetics Laboratory, Department of Biochemistry, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Oncol Rep. 2007 Jun;17(6):1541-9. doi: 10.3892/or.17.6.1541.
Tumour cells have to undergo gene expression changes in order to metastasise and adapt to a new site. We investigated these changes in liver metastases of colorectal cancer by using genome-wide microarray analysis to profile the expression of 48 primary tumours and 28 liver metastases. Statistical analysis of these expression profiles using the significance analysis of microarrays (SAM) method identified 778 genes differentially expressed between primary tumours and metastases. Gene ontology analysis revealed that genes associated with tissue remodelling and immune response were upregulated in metastases relative to primary tumours, whereas genes associated with proliferation and oxidative phosphorylation were downregulated. Quantitative real-time PCR confirmed the differential expression of selected genes, osteopontin, versican, ADAM17, CKS2, PRDX1, CXCR4, CXCL12, and LCN2. The upregulation of genes associated with tissue remodelling and immune response are likely to be involved in metastatic invasion and colonisation of the new site because these genes can promote tumour progression. However, downregulation of genes associated with proliferation suggests that proliferation in metastases was reduced relative to primary tumours.
肿瘤细胞必须经历基因表达变化才能发生转移并适应新的位点。我们通过全基因组微阵列分析对48个原发性肿瘤和28个肝转移灶的表达进行谱分析，研究了结直肠癌肝转移中的这些变化。使用微阵列显著性分析（SAM）方法对这些表达谱进行统计分析，确定了原发性肿瘤和转移灶之间778个差异表达基因。基因本体分析显示，与组织重塑和免疫反应相关的基因在转移灶中相对于原发性肿瘤上调，而与增殖和氧化磷酸化相关的基因下调。定量实时PCR证实了所选基因骨桥蛋白、多功能蛋白聚糖、解聚素金属蛋白酶17（ADAM17）、细胞周期蛋白依赖性激酶亚基2（CKS2）、过氧化物还原酶1（PRDX1）、CXC趋化因子受体4（CXCR4）、CXC趋化因子配体12（CXCL12）和脂质运载蛋白2（LCN2）的差异表达。与组织重塑和免疫反应相关的基因上调可能参与了新位点的转移侵袭和定植，因为这些基因可促进肿瘤进展。然而，与增殖相关基因的下调表明转移灶中的增殖相对于原发性肿瘤有所减少。
