摘要
[目的]探究丙肝肝硬化发展为肝癌的分子机制,为肝癌的早期诊断和治疗提供新思路。[方法]利用生物信息学手段,根据肝硬化和肝癌两种状态下基因间的相关系数变化寻找差异共表达基因,同时筛选甲基化基因,整合miRNA—靶点、转录因子—靶点的调控关系,构建miRNA—转录因子—基因的调控网络并进行拓扑学分析。[结果]确定了肝硬化和肝癌中包含miR-590-3p、TSG101、EGR1、MME在内的主要hub因子。与肝硬化相比,肝癌中的基因间相关系数总体呈下降趋势,hub因子相关的基因间也以相关系数降低为主。[结论]miRNA—转录因子—基因的调控网络可以系统地分析肝癌的分子机制,网络中的hub因子可以作为潜在的肿瘤标志物用于肝癌的早期诊断和治疗。
[Objective] To investigate the molecular mechanism of liver cancer induced by hepatitis C cirrhosis and to provide insights into the early diagnosis and treatment of hepatocellular carcinoma（HCC）.[Methods] The differential co-expression genes were identified by calculating the correlation coefficient between genes associated with hepatitis C cirrhosis and HCC respectively.Meanwhile,the genes,whose methylation level changed during the process of hepatitis C cirrhosis induced HCC,were screened through bioinformatics methodologies.Finally,the related genes and the hepatitis C cirrhosis-associated or HCC-associated miRNA,transcript factors and their targets were integrated to build a transcript regulation network,and meanwhile,the network topology analysis was performed.[Results] Through the network analysis,some primary hub nodes including miR-590-3p,TSG101,EGR1,MME and so on were showed.Additionally,the studies of correlation analysis demonstrated the correlation between genes associated with cirrhosis and HCC integrally presented a decreasing trend when hepatitis C cirrhosis developed into HCC.[Conclusion] The regulation network constructed can be used to analyze the hepatocarcinogenesis mechanisms systematically.The screened hub nodes might be the key potential biomarkers during the hepatocarcinogenesis for early diagnosis and treatment of hepatocellular carcinoma.
出处
《肿瘤学杂志》
CAS
2016年第5期403-409,共7页
Journal of Chinese Oncology
关键词
肝肿瘤
差异共表达
MIRNA
转录因子
甲基化
调控网络
liver neoplasms
differential co-expression
miRNA
transcription factor
methylation
regulatory network
