基于功能模块网络的乙肝病毒和肝癌桥梁分子鉴定。

StephenW

World J Gastroenterol. 2019 Sep 7;25(33):4921-4932. doi: 10.3748/wjg.v25.i33.4921.
Identification of hepatitis B virus and liver cancer bridge molecules based on functional module network.
Huang XB1, He YG1, Zheng L1, Feng H2, Li YM1, Li HY1, Yang FX1, Li J3.
Author information

1
    Department of Hepatobiliary Surgery, Second Hospital Affiliated to Third Military Medical University of Xinqiao Hospital, Chongqing 400037, China.
2
    Division of Nursing, Second Hospital Affiliated to Third Military Medical University, Xinqiao Hospital, Chongqing 400037, China.
3
    Department of Hepatobiliary Surgery, Second Hospital Affiliated to Third Military Medical University of Xinqiao Hospital, Chongqing 400037, China. [email protected].

Abstract
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.
KEYWORDS:

Hepatitis B virus; Hepatocellular carcinoma; Molecular linkage; Transcription factors; non-coding RNA

PMID:
    31543683
PMCID:
    PMC6737318
DOI:
    10.3748/wjg.v25.i33.4921

StephenW

世界J胃肠病学杂志。 2019年9月7日; 25（33）：4921-4932。 doi：10.3748 / wjg.v25.i33.4921。
基于功能模块网络的乙肝病毒和肝癌桥梁分子鉴定。
黄XB1，何YG1，郑L1，冯H2，李YM1，李HY1，杨FX1，李J3。
作者信息

1
第三军医大学附属新桥医院第二医院肝胆外科，重庆400037。
2
第三军医大学附属第二医院护理科，重庆新桥医院，重庆400037。
3
第三军医大学附属新桥医院第二医院肝胆外科，重庆400037。 [email protected]。

抽象
背景：

慢性炎症在癌症发展中的潜在作用已被广泛认可。但是，很少有充分和透彻的研究来探讨乙型肝炎病毒（HBV）和肝细胞癌（HCC）之间的分子联系。
目标：

通过使用多维方法分析HBV-HCC的分子过程，阐明HBV和HCC之间的分子联系。
方法：

首先，通过疾病相关的差异表达基因鉴定出HBV和HCC之间共有的基因失调。其次，基于功能失调基因的蛋白质-蛋白质相互作用网络基于超几何检验确定了一系列功能失调的模块以及模块之间的显着串扰。通过枢轴分析检测关键调节剂。最后，通过模块化方法和药物靶标信息预测了对疾病具有调节作用的靶向药物。
结果：

研究发现，在HBV-HCC过程中有67个基因继续增加。此外，模块网络中的366个重叠基因构建在多个功能块中。可以推测这些基因及其相互作用在炎症和癌症之间的关系中起着重要作用。相应地，大量的串扰为HBV-HCC分子过程构建了模块级桥。另一方面，鉴定了一系列对HBV和HCC具有潜在关键调节作用的非编码RNA和转录因子。一些调节剂在HBV-HCC过程中也存在持续性疾病，包括microRNA-192，microRNA-215和microRNA-874，以及早期生长反应2，FOS和Kruppel样因子4。这些关键是关键桥梁模块外部的分子。最后但并非最不重要的一点是，我们预测，可能会对HBV诱导的HCC产生某些潜在药理或毒性副作用的多种药物，但它们的机制仍需进一步探索。
结论：

结果表明，HBV持续的炎性环境可以作为诱导HCC发生的重要危险因素，这得到了分子证据的支持。
关键词：

肝癌;分子连接；转录因子；非编码RNA

结论：
31543683
PMCID：
PMC6737318
DOI：
10.3748 / wjg.v25.i33.4921