Wang Jaw-Yuan, Yeh Ching-Sheng, Tzou Wen-Shyong, Hsieh Jan-Sing, Chen Fang-Ming, Lu Chien-Yu, Yu Fang-Jung, Cheng Tian-Lu, Huang Tsung-Jen, Lin Shiu-Ru
Department of Surgery, Kaohsiung Medical University, 100, Shin-Chuan 1st Road, Kaohsiung 807, Taiwan, R.O.C.
Oncol Rep. 2005 Jul;14(1):65-72.
The identification of differentially expressed genes has important implications in understanding the biology of colorectal tumorigenesis and progression, as well as developing new diagnostic and therapeutic strategies. In this study, cDNA microarray technology was used to identify colorectal tumor-related functional genes, which are overexpressed continuously from colorectal adenoma to adenocarcinoma. A set of 23 genes with progressive overexpression in the development of colorectal cancer (CRC) was identified by cDNA microarray, then analyzed by sequencing and Northern blot analysis. Validation of our array results was simultaneously performed by exploring the SAGEmap database. Furthermore, the gradually over-expressed genes from adenoma to adenocarcinoma were validated by Northern blot analysis with additional samples from three patients with synchronous colorectal adenocarcinoma and adenoma and four patients with CRC. Of these 23 genes, one was a function-unknown gene, designated as Homo sapiens chromosome 21q22.1 anonymous mRNA sequence (Genbank accession no. AF003738), and 22 were function-known genes. Searching through the Gene Ontology Browser at the Cancer Genome Analysis Project website revealed that the biological roles of these 22 function-known genes are involved in cell motility, cell adhesion, chemokine activity, signal transduction, cytoskeleton organization, proteolysis, apoptosis, and cell proliferation. The genes identified in the present study offer valuable information on colorectal carcinogenesis and metastasis, and represent a potential source of novel targets for new strategies for CRC diagnosis and therapy.
差异表达基因的鉴定对于理解结直肠癌发生和发展的生物学机制以及开发新的诊断和治疗策略具有重要意义。在本研究中,利用cDNA微阵列技术鉴定从结直肠腺瘤到腺癌持续过度表达的结直肠肿瘤相关功能基因。通过cDNA微阵列鉴定出一组在结直肠癌(CRC)发生过程中呈渐进性过度表达的23个基因,随后进行测序和Northern印迹分析。通过探索SAGEmap数据库同时对我们的阵列结果进行验证。此外,利用来自3例同步结直肠腺瘤和腺癌患者以及4例CRC患者的额外样本,通过Northern印迹分析对从腺瘤到腺癌逐渐过度表达的基因进行验证。在这23个基因中,1个是功能未知基因,命名为智人染色体21q22.1匿名mRNA序列(Genbank登录号AF003738),22个是功能已知基因。通过癌症基因组分析项目网站的基因本体浏览器搜索发现,这22个功能已知基因的生物学作用涉及细胞运动、细胞黏附、趋化因子活性、信号转导、细胞骨架组织、蛋白水解、细胞凋亡和细胞增殖。本研究中鉴定出的基因提供了结直肠癌发生和转移的有价值信息,并代表了CRC诊断和治疗新策略潜在的新靶点来源。