Organ Transplant Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, Guangdong, China.
BMC Infect Dis. 2020 Jan 29;20(1):84. doi: 10.1186/s12879-019-4720-x.
Hepatitis B virus (HBV) infection is a global health problem and interferon-alpha (IFN-α) is one of the effective therapies. However, little is known about the genetic background of the HBV infection or the genetic determinants of the IFN-α treatment response. Thus, we aim to explore the possible molecular mechanisms of HBV infection and its response to the IFN-α therapy with a comprehensive bioinformatics analysis.
The Gene Expression Omnibus datasets (GSE83148, GSE84044 and GSE66698) were collected and the differentially expressed genes (DEGs), key biological processes and intersecting pathways were analyzed. The expression of the co-expressed DEGs in the clinical samples was verified by quantitative real time polymerase chain reaction (qRT-PCR).
Analysis of all the 3 datasets revealed that there were eight up-regulated and one down-regulated co-expressed DEGs following the HBV infection and after IFN-α treatment. In clinical samples, the mRNA level of HKDC1, EPCAM, GSN, ZWINT and PLD3 were significantly increased, while, the mRNA level of PLEKHA2 was significantly decreased in HBV infected liver tissues compared to normal liver tissues. PI3K-Akt signaling pathway, focal adhesion, HTLV-I infection, cytokine-cytokine receptor interaction, metabolic pathways, NF-κB signaling pathway were important pathways associated with the HBV infection and the response of IFN-α treatment.
The co-expressed genes, common biological processes and intersecting pathways identified in the study might play an important role in HBV infection and response of IFN-α treatment. The dysregulated genes may act as novel biomarkers and therapeutic targets for HBV.
乙型肝炎病毒(HBV)感染是一个全球性的健康问题,干扰素-α(IFN-α)是一种有效的治疗方法。然而,对于 HBV 感染的遗传背景或 IFN-α 治疗反应的遗传决定因素知之甚少。因此,我们旨在通过综合生物信息学分析来探讨 HBV 感染及其对 IFN-α治疗反应的可能分子机制。
收集基因表达综合数据集(GSE83148、GSE84044 和 GSE66698),分析差异表达基因(DEGs)、关键生物学过程和相交途径。通过定量实时聚合酶链反应(qRT-PCR)验证临床样本中共同表达 DEGs 的表达。
对所有 3 个数据集的分析表明,HBV 感染后和 IFN-α 治疗后存在 8 个上调和 1 个下调的共同表达 DEGs。在临床样本中,与正常肝组织相比,HBV 感染肝组织中 HKDC1、EPCAM、GSN、ZWINT 和 PLD3 的 mRNA 水平显著升高,而 PLEKHA2 的 mRNA 水平显著降低。与 HBV 感染和 IFN-α 治疗反应相关的重要途径包括 PI3K-Akt 信号通路、黏附斑、HTLV-I 感染、细胞因子-细胞因子受体相互作用、代谢途径、NF-κB 信号通路。
本研究中鉴定的共同表达基因、共同的生物学过程和相交途径可能在 HBV 感染和 IFN-α 治疗反应中起重要作用。失调基因可作为 HBV 的新型生物标志物和治疗靶点。