基于差异性表达谱分析挖掘不同亚型鼻咽癌的保护性转录因子  

Differential gene expression profiling for identification of protective transcription factors in different subtypes of nasopharyngeal carcinoma

作　　者：黄春月[1] 林沛[2] 汪佳宏[2] 黄仲曦[2] 

机构地区：[1]南方医科大学第一临床医学院2007级八年制 [2]南方医科大学肿瘤研究所,广东广州510515

出　　处：《南方医科大学学报》2013年第11期1565-1570,共6页Journal of Southern Medical University

基　　金：国家自然科学基金863课题(2006AA02A404)~~

摘　　要：目的探究41例鼻咽组织活检样本中差异基因表达谱所显示的失调基因及挖掘调控这些基因的转录因子。方法利用EXCEL及生物信息学方法分析Ⅰ、Ⅱ型鼻咽癌(NPC)患者鼻咽组织活检样本中差异表达基因谱,挖掘出同时符合以下条件的转录因子:(1)在两组差异表达基因的结合位点具有统计学意义;(2)鼻咽组织中转录因子与基因的表达存在相关性;(3)相关基因的表达至少有40%是受转录因子影响的。结果在Ⅰ型NPC较Ⅱ型NPC上调的差异表达基因谱("Ⅰ_Ⅱ_Up")中,找到对应的符合条件的转录因子有80个。其中RUNX3、GATA3、NR3C1、NRF1、RXRA、SMAD7、TBP、ZBTB6等8个正调节因子和HLF、MTF1等2个负调节因子,它们调控与T细胞受体信号通路相关的基因。然而在Ⅰ型NPC较Ⅱ型NPC下调的差异表达基因谱("Ⅰ_Ⅱ_Down")中,未找到符合条件的转录因子。结论通过分析Ⅰ、Ⅱ型NPC患者鼻咽组织活检样本的差异表达基因谱发现,Ⅰ型NPC(NPC_Ⅰ)患者的差异表达基因主要与机体免疫反应相关,利用EXCEL及生物信息学方法,挖掘出8个正调节因子和2个负调节因子,主要调控与T细胞受体信号通路相关的基因。预测到的这10个转录因子有可能成为药物研发的新靶点,通过增强机体免疫防御能力,有望提高NPC患者的生存率。但研究中未能发现与"Ⅰ_Ⅱ_Down"基因谱明显相关的转录因子,这可能与NPC_Ⅱ患者差异表达基因受转录因子、DNA修饰、磷酸化、染色体变异、环境等多因素影响有关。Objective To analyze the dysregulated genes among the differentially expressed genes in 41 nasopharyngeal biopsy samples and identify their protective transcriptional factors. Methods The differentially expressed gene profiles were obtained by analyzing both types I and II nasopharyngeal carcinoma （NPC_I and NPC_II, respectively） using EXCEL and Bioinformatics tools. The transcriptional factors were further studied only when （1） the difference in the binding sites of the differentially expressed genes between NPC_I and NPC_II groups was statistically significant, （2） the expressions of the transcription factors were correlated with the gene expressions in the samples, and （3） the transcription factors affected at least 40% of the expression of the related genes. Results In NPC_I samples, 80 transcription factors were found to be up-regulated, in which RUNX3, GATA3, NR3C1, NRF1, RXRA, SMAD7, TBP, and ZBTB6 were positive factors and HLF and MTF1 were negative factors, involved in the regulation of the genes in T cell receptor signaling pathway. No eligible transcription factors were found in assodation with down-regulated genes in NPC_I compared to NPC_II gene expression profiles. Conclusions The over-expressed genes in NPC_I are mainly related to immune responses, and we found 8 positive factors and 2 negative factors that regulate the genes in T cell receptor signaling pathway. The 10 transcription factors may serve as potential therapeutic targets for NPC_I. We failed to identify any transcription factors associated with down-regulated genes in NPC_I relative to NPC_II possibly as a result of multiple factors that affect the differential gene expressions in NPC_II including the transcription factors, DNA phosphorylation and modification, chromosome variation and environmental factors.

关 键 词：鼻咽癌 免疫防御 保护性转录因子 生存率 

分 类 号：R739.63[医药卫生—肿瘤]