通过文本挖掘和大数据分析全面审查乙型肝炎病毒相关肝细

StephenW

Biol Rev Camb Philos Soc. 2018 Aug 13. doi: 10.1111/brv.12457. [Epub ahead of print]
Comprehensive review of Hepatitis B Virus-associated hepatocellular carcinoma research through text mining and big data analytics.
Lee WY1,2, Bachtiar M1,3, Choo CCS2,3, Lee CG1,2,3,4.
Author information

1
    Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119077, Singapore.
2
    NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, 119077, Singapore.
3
    Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore.
4
    Duke-National University of Singapore Graduate Medical School, Singapore, 169547, Singapore.

Abstract

PubMed was text mined to glean insights into the role of Hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) from the massive number of publications (9249) available to date. Reports from ∼70 countries identified >1300 human genes associated with either the Core, Surface or X gene in HBV-associated HCC. One hundred and forty-three of these host genes, which can potentially yield 1180 biomolecular interactions, each were reported in at least three different publications to be associated with the same HBV. These 143 genes function in 137 pathways, involved mainly in the cell cycle, apoptosis, inflammation and signalling. Fourteen of these molecules, primarily transcriptional regulators or kinases, play roles in several pathways pertinent to the hallmarks of cancers. 'Chronic' was the most frequent word used across the 9249 abstracts. A key event in chronic HBV infection is the integration of HBV into the host genome. The advent of cost-effective, next-generation sequencing technology facilitated the employment of big-data analytics comprehensively to characterize HBV-host integration within HCC patients. A total of 5331 integration events were reported across seven publications, with most of these integrations observed between the Core/X gene and the introns of genes. Nearly one-quarter of the intergenic integrations are within repeats, especially long interspersed nuclear elements (LINE) repeats. Integrations within 13 genes were each reported by at least three different studies. The human gene with the most HBV integrations observed is the TERT gene where a total of 224 integrations, primarily at its promoter and within the tumour tissue, were reported by six of seven publications. This unique review, which employs state-of-the-art text-mining and data-analytics tools, represents the most complete, systematic and comprehensive review of nearly all the publications associated with HBV-associated HCC research. It provides important resources to either focus future research or develop therapeutic strategies to target key molecules reported to play important roles in key pathways of HCC, through the systematic analyses of the commonly reported molecules associated with the various HBV genes in HCC, including information about the interactions amongst these commonly reported molecules, the pathways in which they reside as well as detailed information regarding the viral and host genes associated with HBV integration in HCC patients. Hence this review, which highlights pathways and key human genes associated with HBV in HCC, may facilitate the deeper elucidation of the role of HBV in hepato-carcinogenesis, potentially leading to timely intervention against this deadly disease.
KEYWORDS:

AKT/PI3K/MAPK; FN1; HBV; HBx; HCC; TERT; chronic; integration; liver cancer; text-mining

PMID:
    30105774
DOI:
    10.1111/brv.12457

StephenW

Biol Rev Camb Philos Soc。 2018年8月13日.doi：10.1111 / brv.12457。 [提前打印]
通过文本挖掘和大数据分析全面审查乙型肝炎病毒相关肝细胞癌研究。
Lee WY1,2，Bachtiar M1,3，Choo CCS2,3，Lee CG1,2,3,4。
作者信息

1
    新加坡国立大学Yong Loo Lin医学院生物化学系，新加坡，119077，新加坡。
2
    新加坡国立大学综合科学与工程研究生院，新加坡，119077，新加坡。
3
    新加坡国立癌症中心Humphrey Oei癌症研究所医学科，新加坡11 Hospital Drive，169610，新加坡。
4
    Duke-Singapore University of Singapore University Graduate School，Singapore，169547，新加坡。

抽象

PubMed的文本是从迄今为止可获得的大量出版物（9249）中收集的关于乙型肝炎病毒（HBV）在肝细胞癌（HCC）中的作用的见解。来自约70个国家的报告确定了与HBV相关的HCC中的核心，表面或X基因相关的> 1300个人类基因。这些宿主基因中的一百四十三个可以潜在地产生1180个生物分子相互作用，每个在至少三个不同的出版物中报道与相同的HBV相关。这143个基因在137个途径中起作用，主要涉及细胞周期，细胞凋亡，炎症和信号传导。这些分子中的14种，主要是转录调节因子或激酶，在与癌症标志相关的几种途径中发挥作用。 “慢性”是9249摘要中最常用的词。慢性HBV感染的关键事件是HBV整合到宿主基因组中。经济高效的新一代测序技术的出现促进了大数据分析的全面应用，以表征HCC患者中HBV宿主整合的特征。在7个出版物中共报告了5331个整合事件，其中大多数这些整合在Core / X基因和基因内含子之间观察到。近四分之一的基因间整合在重复内，特别是长穿插核元素（LINE）重复。通过至少三个不同的研究报告了13个基因内的整合。观察到具有最多HBV整合的人类基因是TERT基因，其中七个出版物中的六个报告了总共224个整合，主要在其启动子和肿瘤组织内。这一独特的评论采用了最先进的文本挖掘和数据分析工具，代表了对与HBV相关的HCC研究相关的几乎所有出版物的最完整，系统和全面的评论。它通过对与HCC中各种HBV基因相关的常见报道分子的系统分析，包括有关的信息，提供重点资源，既可以集中未来的研究，也可以制定治疗策略，以靶向报告在HCC关键途径中发挥重要作用的关键分子。这些常见报道分子之间的相互作用，它们所处的途径以及与HCC患者中HBV整合相关的病毒和宿主基因的详细信息。因此，该综述突出了HCC中与HBV相关的途径和关键人类基因，可能有助于更深入地阐明HBV在肝癌发生中的作用，可能导致对这种致命疾病的及时干预。
关键词：

AKT / PI3K / MAPK; FN1; HBV; HBx蛋白; HCC; TERT;慢性;积分;肝癌;文本挖掘

结论：
    30105774
DOI：
    10.1111 / brv.12457