Published online Sep 7, 2019. doi: 10.3748/wjg.v25.i33.4921
Peer-review started: April 25, 2019
First decision: May 30, 2019
Revised: June 29, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: September 7, 2019
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).
To conduct a comprehensive and in-depth discussion on the bridge mechanism between HBV and HCC.
The purpose of this study was to explore the co-imbalance bridging molecules between HBV and HCC and their potential drugs based on the dysfunction module.
First, maladjusted genes shared between HBV and HCC were identified by disease-related DEGs. Second, the PPI 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.
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 ncRNAs and TFs 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 miRNA-192, miRNA-215, and miRNA-874, and EGR2, FOS, and KLF4. 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 need to be further explored.
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.
In the future, research may comprehensively and thoroughly explore the mechanism of HCC occurrence and development and predict the potential therapeutic methods and mechanisms.