Identification of hepatitis B virus and liver cancer bridge molecules based on functional module network

摘要

BACKGROUND The potential role of chronic inflammation in the development of cancer has been widely recognized.However,there has been little research fully and thoroughly exploring the molecular link between hepatitis B virus(HBV)and hepatocellular carcinoma(HCC).AIM To elucidate the molecular links between HBV and HCC through analyzing the molecular processes of HBV-HCC using a multidimensional approach.METHODS First,maladjusted genes shared between HBV and HCC were identified by disease-related differentially expressed genes.Second,the protein-protein interaction network based on dysfunctional genes identified a series of dysfunctional modules and significant crosstalk between modules based on the hypergeometric test.In addition,key regulators were detected by pivot analysis.Finally,targeted drugs that have regulatory effects on diseases were predicted by modular methods and drug target information.RESULTS The study found that 67 genes continued to increase in the HBV-HCC process.Moreover,366 overlapping genes in the module network participated in multiple functional blocks.It could be presumed that these genes and their interactions play an important role in the relationship between inflammation and cancer.Correspondingly,significant crosstalk constructed a module level bridge for HBV-HCC molecular processes.On the other hand,a series of non-coding RNAs and transcription factors that have potential pivot regulatory effects on HBV and HCC were identified.Among them,some of the regulators also had persistent disorders in the process of HBV-HCC including microRNA-192,microRNA-215,and microRNA-874,and early growth response 2,FOS,and Kruppel-like factor 4.Therefore,the study concluded that these pivots are the key bridge molecules outside the module.Last but not least,a variety of drugs that may have some potential pharmacological or toxic side effects on HBV-induced HCC were predicted,but their mechanisms still need to be further explored.CONCLUSION The results suggest that the persistent inflammatory environment of HBV can be utilized as an important risk factor to induce the occurrence of HCC,which is supported by molecular evidence.