基因表达谱芯片在非霍奇金淋巴瘤发病机制研究中的应用

cDNA microarray in the research of lymphomagenesis of NHL

目的:为了较全面地了解非霍奇金淋巴瘤(NHL)基因组的表达情况,研究其可能发病机制以筛选淋巴瘤相关基因,为今后的研究工作提供靶点。方法:利用基因表达谱芯片(包括8398个人类基因)分别比较B、T细胞NHL与非肿瘤性淋巴结组织的基因表达情况,筛选出2组共同有差异表达的基因进行聚类分析,探讨该基因群与NHL可能的内在联系。结果:以表达相差2倍以上为标准,筛选出2组均有差异表达的基因248条,其中已知基因173条,上调104条,下调69条。在这些基因中,细胞周期相关蛋白基因PCNA、CDC2、CCB1均上调,提示淋巴瘤细胞处于高增殖状态,G2/M交界处关键调控蛋白CDC2、CCB1和纺锤体组装检查点MAD2、BUB1B基因上调,提示它们的异常可能是淋巴瘤重要的发病环节。p53基因和Erk3/cPLA2基因下调,提示它们介导的凋亡途径受到抑制。结论:增殖和凋亡之间的失平衡是淋巴瘤的可能发病机制之一,细胞周期中G2/M交界点CDC2/CCB1复合物和纺锤体装配检查点调控蛋白活性异常可能是这种失平衡的重要作用环节。

Objective：To comprehensively understand the NHL gene expression pattern, and to investigate the lymphomagenesis of NHL in order to find the lymphoma--associated genes and to assist the further research of lymphoma. Method：cDNA microarray （including 8398 human genes） was used to detect the different gene expres- sion between B-, T-cell NHL and non-neoplastic lymph node tissue. We detected and analysis the significant changes in the gene expression of NHL cells. The possibility of involvement of the specially expressed genes in NHL was discussed. Result： Two times of gene expression difference was selected as the screen standard. 248 genes were found expressed differen＇dy between these two groups. In 173 genes which were known, an increased expression level was found in 104 and a decreased in 69 genes. Among these genes, we found a strong increase in the genes encoding cell cycle related proteins, PCNA, CDC2, CCB1, demonstrating hyperproliferation of lympho- ma cells. CDC2/CCB1 Complex which was the key regulation protein of G2/M transition, and MAD2/BUB1B which was the checkpoint of spindle assembly was also up-regulated, indicating that these gene may play the essential role in lymphoma. Down-regulation of P53 gene and Erk3/cPLA2 gene suggested the inhibition of apoptosis pathway induced by these genes. Conclusion： An imbalance between cellular proliferation and apoptosis maybe critical for the pathogenesis of lymphoma. In the cell cycle, the abnormal activity of CDC2/CCB1 Complex and the checkpoint of spindle assembly may play the essential role in lymphoma, cDNA microarray is an effective method for rapidly screening tumor-associated genes in order to obtain more special gene markers for clinical application.