南方医科大学学报

南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (11): 1565-.

• • 上一篇    下一篇

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

黄春月，林沛，汪佳宏，黄仲曦   

  • 出版日期:2013-11-20 发布日期:2013-11-20

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

  • Online:2013-11-20 Published:2013-11-20

PDF

1043

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。

Abstract: 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 association 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, DNAphosphorylation and modification, chromosome variation and environmental factors.