Please use this identifier to cite or link to this item: https://doi.org/10.1111/brv.12457
Title: Comprehensive review of Hepatitis B Virus-associated hepatocellular carcinoma research through text mining and big data analytics
Authors: Lee, Wai Yeow
Bachtiar, Maulana 
Choo, Cheryl CS
Lee, Caroline G 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
liver cancer
HBV
HCC
text-mining
chronic
integration
HBx
AKT/PI3K/MAPK
TERT
FN1
CYCLIN-A EXPRESSION
C-MYC
DNA INTEGRATION
GENOME BROWSER
UP-REGULATION
X-GENE
PROTEIN
MUTATIONS
CELLS
TUMOR
Issue Date: 1-Apr-2019
Publisher: WILEY
Citation: Lee, Wai Yeow, Bachtiar, Maulana, Choo, Cheryl CS, Lee, Caroline G (2019-04-01). Comprehensive review of Hepatitis B Virus-associated hepatocellular carcinoma research through text mining and big data analytics. BIOLOGICAL REVIEWS 94 (2) : 353-367. ScholarBank@NUS Repository. https://doi.org/10.1111/brv.12457
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.
Source Title: BIOLOGICAL REVIEWS
URI: https://scholarbank.nus.edu.sg/handle/10635/226866
ISSN: 14647931
1469185X
DOI: 10.1111/brv.12457
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