鼻咽癌凋亡及增生相关基因筛选与分析

Screening and preliminary analysis of the apoptosis- and proliferation-related genes in nasopharyngeal carcinoma

目的筛选及分析鼻咽癌发生发展过程中的细胞凋亡相关基因及增生相关基因。方法结合GO分类从本实验室已有的鼻咽癌基因芯片数据中筛选异常表达的细胞凋亡相关基因及细胞增生相关基因;根据鼻咽癌发生发展的树模型提示的三个阶段,找出各阶段的鼻咽癌细胞凋亡相关基因及细胞增生相关基因;再结合文献进一步分析两种基因在鼻咽癌发生树模型中的分布特点及规律。结果鼻咽癌细胞凋亡相关基因19个,其中处于染色体丢失区段的下调鼻咽癌细胞凋亡相关基因9个(DNASE1L3等)、处于染色体扩增区段的上调鼻咽癌细胞凋亡相关基因10个(DEDD等)。鼻咽癌细胞增生相关基因21个,其中处于染色体丢失区段的下调鼻咽癌细胞增生相关基因8个(TUSC2等)、处于染色体扩增区段的上调鼻咽癌细胞增生相关基因13个(EMP1等)。处于染色体丢失区段的下调鼻咽癌细胞凋亡相关基因多参与诱导或调控细胞凋亡;而处于染色体扩增区段的上调鼻咽癌细胞增生相关基因多参与正调控细胞增生。结论鼻咽癌可能存在两种发生方式:一种以凋亡受抑为主要原因;另一种以增生过度为主要原因。

Objective To screen and analyze the apoptosis- and proliferation-related genes in human nasopharyngeal carcinoma （NPC）. Methods According to gene ontology classification, the abnormal expressions of the genes related to cell apoptosis and proliferation were identified in the NPC gene chip data. The cell apoptosis- and proliferation-related genes expressed in each of the 3 stages, as defined by the tree model for the pathogenesis and progression of NPC, were screened, and with literature review, their distribution in the tree model were analyzed. Results Nineteen genes related to cell apoptosis were found in NPC, among which 9 were down-regulated （such as DNASEIL3） and located in the chromosome deletion regions, and 10 were up-regulated （such as DEDD） in the chromosome amplification regions. Twenty-one cell proliferation-related genes were identified, including 8 down-regulated genes （such as TUSC2） in the chromosome deletion regions and 13 up-regulated ones （such as EMP1） in the chromosome amplification regions. In the chromosome deletion regions, the down-regulated cell apoptosis-related genes participated mostly in inducing and regulating cell apoptosis, and the up-regulated cell proliferation-related genes in the chromosome amplification regions were mostly associated with the positive regulation of cell proliferation. Conclusion NPC occurs possibly through two pathways by inhibiting cell apoptosis or by promoting excessive cell proliferation.