转录组分析和病毒-人相互作用组洞察hbv驱动的肝细胞癌的致癌改变。

IF 1.9 4区 医学 Q4 IMMUNOLOGY
Anilkumar I Ananthakrishnan, Althaf Mahin, Thottethodi Subrahmanya Keshava Prasad, Chandran S Abhinand
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引用次数: 0

摘要

肝细胞癌(HCC)是肝癌的主要形式,由于其发病率不断上升和病因多样,引起了重大的全球健康问题。乙型肝炎病毒(HBV)引起的慢性感染是影响HCC发展的重要病因。尽管多组学方法的最新进展促进了对HCC分子特征的广泛探索,但由于样本量有限和早期检测的分类器复杂等参数,将亚型特征转化为临床应用一直具有挑战性。在本研究中,我们对hbv感染的HCC患者组织数据进行转录组学分析,以全面了解hbv相关HCC的复杂分子机制,特别是影响癌基因表达的病毒蛋白相互作用。在两个GEO数据集中鉴定的1059个差异表达基因(DEGs)显示细胞周期和有丝分裂相关基因上调,同时参与脂肪酸降解和细胞色素P450活性的基因下调。CDK1和CDC20是相互作用组分析中top cluster和hub基因的一部分,通过基因表达模式和总生存分析确定为hbv阳性HCC的潜在标志物。此外,在HCC发展中具有重要意义的19个deg被确定为HBV蛋白的相互作用伙伴。其中,HBsAg与ALB和SHBG的相互作用及其下调与HBV和HCC患者睾酮水平较低相关。总之,该研究增强了对hbv阳性HCC的异质性和分子发病机制的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transcriptome Profiling and Viral-Human Interactome Insights Into HBV-Driven Oncogenic Alterations in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the primary form of liver cancer that poses a significant global health concern due to its increasing incidence rates and diverse etiology. Chronic infection induced by hepatitis B virus (HBV) is a prominent etiological factor influencing the development of HCC. Although recent advances in multi-omics approaches have facilitated extensive exploration of HCC molecular characteristics, translating the characteristics of subtypes into clinical applications has been challenging due to parameters like limited sample size and complex classifiers for early detection. In the present study, we performed transcriptomics profiling of HBV-infected HCC patient tissue data to gather comprehensive insights into the intricate molecular mechanisms underlying HBV-associated HCC, specifically, viral protein interactions that influence the expression of oncogenes. The 1059 differentially expressed genes (DEGs) identified across two GEO data sets revealed upregulation of cell cycle and mitosis-related genes, alongside downregulation of genes involved in fatty acid degradation and cytochrome P450 activity. CDK1 and CDC20 which are part of the top cluster and hub gene from interactome analysis were identified as potential markers for HBV-positive HCC through gene expression pattern and overall survival analysis. Additionally, 19 DEGs showing significance in HCC development were identified as interacting partners with HBV proteins. Among them, the interaction of HBsAg with ALB and SHBG and their downregulation correlates to the lower testosterone levels identified in HBV and HCC patients. Together, the study enhances the understanding of the heterogeneity and molecular pathogenesis of HBV-positive HCC.

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来源期刊
Microbiology and Immunology
Microbiology and Immunology 医学-免疫学
CiteScore
5.20
自引率
3.80%
发文量
78
审稿时长
1 months
期刊介绍: Microbiology and Immunology is published in association with Japanese Society for Bacteriology, Japanese Society for Virology, and Japanese Society for Host Defense Research. It is peer-reviewed publication that provides insight into the study of microbes and the host immune, biological and physiological responses. Fields covered by Microbiology and Immunology include:Bacteriology|Virology|Immunology|pathogenic infections in human, animals and plants|pathogenicity and virulence factors such as microbial toxins and cell-surface components|factors involved in host defense, inflammation, development of vaccines|antimicrobial agents and drug resistance of microbes|genomics and proteomics.
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