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pmid:31322223

DNA hypermethylation of aurora kinase A in hepatitis C virus‑positive hepatocellular carcinoma.

Zuohong Ma · Yefu Liu · Zhiqiang Hao · Xiangdong Hua · Wenxin Li

Molecular medicine reports · 2019 doi:10.3892/mmr.2019.10487

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

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paper object · 10 fields
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title
DNA hypermethylation of aurora kinase A in hepatitis C virus‑positive hepatocellular carcinoma.
doi
10.3892/mmr.2019.10487
pmid
31322223
authors array · 5 items
[0]
Zuohong Ma
[1]
Yefu Liu
[2]
Zhiqiang Hao
[3]
Xiangdong Hua
[4]
Wenxin Li
journal
Molecular medicine reports
year
2019
abstract
Changes in the methylation levels of tumor suppressor genes or proto‑oncogenes are involved in the pathogenesis of hepatitis C virus (HCV) infection‑induced hepatocellular carcinoma (HCC). The aim of the present study was to identify novel aberrantly methylated differentially expressed genes by integrating mRNA expression profile (GSE19665 and GSE62232) and methylation profile (GSE60753) microarrays downloaded from the Gene Expression Omnibus database. Functional enrichment analysis of screened genes was performed using the DAVID software and BinGO database. Protein‑protein interaction (PPI) networks were constructed using the STRING database, followed by module analysis with MCODE software. The transcriptional and translational expression levels of crucial genes were confirmed using The Cancer Genome Atlas (TCGA) datasets and Human Protein Atlas database (HPA). A total of 122 downregulated/hypermethylated genes and 63 upregulated/hypomethylated genes were identified. These genes were enriched in the Gene Ontology biological processes terms of 'inflammatory response' [Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS)] and 'cell cycle process' [aurora kinase A (AURKA), cyclin dependent kinase inhibitor 3 (CDKN3) and ubiquitin conjugating enzyme E2 C (UBE2C)]. PPI network and module analysis indicated that human oncogenes FOS, AURKA, CDKN3 and UBE2C may be hub genes. mRNA, protein expression and methylation levels of AURKA and FOS were validated by TCGA and HPA data. In conclusion, aberrantly methylated AURKA and FOS may be potential therapeutic targets for HCV‑positive HCC.
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Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between HCV-positive HCC and control samples were identified using the Linear Models for Microarray Data method (version 3.34.0; http://bioconductor.org/packages/release/bioc/html/limma.html) (15) in the Bioconductor R package.
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sections[6] "Differential gene expression and methylation analysis" paragraph 2
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Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between HCV-positive HCC and control samples were identified using the Linear Models for Microarray Data method (version 3.34.0; http://bioconductor.org/packages/release/bioc/html/limma.html) (15) in the Bioconductor R package.
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The sequencing datasets GSE19665 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19665), GSE62232 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62232) and GSE60753 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60753) were downloaded from the GEO database in NCBI. The mRNA and microRNA sequencing data were obtained from The Cancer Genome Atlas (https://tcga-data.nci.nih.gov).
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sections[19] "Availability of data and materials" paragraph 2
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The sequencing datasets GSE19665 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19665), GSE62232 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62232) and GSE60753 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60753) were downloaded from the GEO database in NCBI. The mRNA and microRNA sequencing data were obtained from The Cancer Genome Atlas (https://tcga-data.nci.nih.gov).
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Aberrant DNA methylation in hepatitis B and C virus-related hepatocellular carcinoma
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Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between HCV-positive HCC and control samples were identified using the Linear Models for Microarray Data method (version 3.34.0; http://bioconductor.org/packages/release/bioc/html/limma.html) (15) in the Bioconductor R package.
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method-2
family
network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
PPI
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 3 items
[0]
GSE19665
[1]
GSE62232
[2]
GSE60753
resolved_accessions array · 3 items
[0]
GSE19665
[1]
GSE62232
[2]
GSE60753
statements array · 1 item
[0]
The sequencing datasets GSE19665 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19665), GSE62232 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62232) and GSE60753 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60753) were downloaded from the GEO database in NCBI. The mRNA and microRNA sequencing data were obtained from The Cancer Genome Atlas (https://tcga-data.nci.nih.gov).
basis
The paper names GSE19665, GSE62232, GSE60753 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 2 items
[0]
source:pmid:31322223
[1]
data:geo:GSE19665
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE19665
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:15:48Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
17862
completion_tokens
2850
cached_tokens
779
stages array · 1 item
[0] object · 4 fields
id
extraction
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complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
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null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:31322223
type
paper
label
pmid:31322223
[1] object · 3 fields
id
source:pmid:31322223
type
manuscript
label
PMID 31322223 full text
[2] object · 3 fields
id
data:geo:GSE19665
type
dataset
label
GEO GSE19665
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:31322223
type
paper
label
pmid:31322223
[1] object · 3 fields
id
source:pmid:31322223
type
manuscript
label
PMID 31322223 full text
[2] object · 3 fields
id
data:geo:GSE19665
type
dataset
label
GEO GSE19665
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-31322223
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extraction
used array · 1 item
[0]
source:pmid:31322223
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agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE19665
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE19665
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
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software
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Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
label
MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:31322223
parent_hash
sha256:d5f2d5b086378cd9e277491c52b35642422b785ec2aaa018a0cbe0887a37873e
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null
gaps array · 10 items
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asset:data:geo:GSE19665 licence not read
[1]
asset:data:geo:GSE19665 not downloaded
[2]
asset:data:geo:GSE60753 licence not read
[3]
asset:data:geo:GSE60753 not downloaded
[4]
asset:data:geo:GSE62232 licence not read
[5]
asset:data:geo:GSE62232 not downloaded
[6]
execution.not_run
[7]
review.human_critique
[8]
review.independent_reader
[9]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
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differential_expression
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f2132e96ae6c7a4e
required_operations array · 3 items
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[1]
differential_expression_fit
[2]
fdr_bh
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supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between HCV-positive HCC and control samples were identified using the Linear Models for Microarray Data method (version 3.34.0; http://bioconductor.org/packages/release/bioc/html/limma.html) (15) in the Bioconductor R package.
order_basis
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assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31322223", "kind": "science-record", "revision": 8, "content_hash": "sha256:58f7bad64d1c33cb32111f9a88c2666a218efb172ac057fdf0534fbe69404e87", "created_at": "2026-11-01T15:40:47Z", "updated_at": "2026-11-01T22:44:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "DNA hypermethylation of aurora kinase A in hepatitis C virus‑positive hepatocellular carcinoma.", "doi": "10.3892/mmr.2019.10487", "pmid": "31322223", "authors": ["Zuohong Ma", "Yefu Liu", "Zhiqiang Hao", "Xiangdong Hua", "Wenxin Li"], "journal": "Molecular medicine reports", "year": 2019, "abstract": "Changes in the methylation levels of tumor suppressor genes or proto‑oncogenes are involved in the pathogenesis of hepatitis C virus (HCV) infection‑induced hepatocellular carcinoma (HCC). The aim of the present study was to identify novel aberrantly methylated differentially expressed genes by integrating mRNA expression profile (GSE19665 and GSE62232) and methylation profile (GSE60753) microarrays downloaded from the Gene Expression Omnibus database. Functional enrichment analysis of screened genes was performed using the DAVID software and BinGO database. Protein‑protein interaction (PPI) networks were constructed using the STRING database, followed by module analysis with MCODE software. The transcriptional and translational expression levels of crucial genes were confirmed using The Cancer Genome Atlas (TCGA) datasets and Human Protein Atlas database (HPA). A total of 122 downregulated/hypermethylated genes and 63 upregulated/hypomethylated genes were identified. These genes were enriched in the Gene Ontology biological processes terms of 'inflammatory response' [Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS)] and 'cell cycle process' [aurora kinase A (AURKA), cyclin dependent kinase inhibitor 3 (CDKN3) and ubiquitin conjugating enzyme E2 C (UBE2C)]. PPI network and module analysis indicated that human oncogenes FOS, AURKA, CDKN3 and UBE2C may be hub genes. mRNA, protein expression and methylation levels of AURKA and FOS were validated by TCGA and HPA data. In conclusion, aberrantly methylated AURKA and FOS may be potential therapeutic targets for HCV‑positive HCC.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between HCV-positive HCC and control samples were identified using the Linear Models for Microarray Data method (version 3.34.0; http://bioconductor.org/packages/release/bioc/html/limma.html) (15) in the Bioconductor R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31322223", "locator": "sections[6] \"Differential gene expression and methylation analysis\" paragraph 2", "quote": "Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between HCV-positive HCC and control samples were identified using the Linear Models for Microarray Data method (version 3.34.0; http://bioconductor.org/packages/release/bioc/html/limma.html) (15) in the Bioconductor R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The sequencing datasets GSE19665 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19665), GSE62232 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62232) and GSE60753 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60753) were downloaded from the GEO database in NCBI. The mRNA and microRNA sequencing data were obtained from The Cancer Genome Atlas (https://tcga-data.nci.nih.gov).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31322223", "locator": "sections[19] \"Availability of data and materials\" paragraph 2", "quote": "The sequencing datasets GSE19665 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19665), GSE62232 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62232) and GSE60753 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60753) were downloaded from the GEO database in NCBI. The mRNA and microRNA sequencing data were obtained from The Cancer Genome Atlas (https://tcga-data.nci.nih.gov)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31322223"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE19665"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE19665"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31322223", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3892/mmr.2019.10487", "sha256": "sha256:22f96d179356c107d1bd6e23efdac103a6a06cb22784edf12c648ce4cb695537", "bytes": 23231, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3892/mmr.2019.10487", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6691273", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE19665", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19665", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE19665", "version": null, "note": "The sequencing datasets GSE19665 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19665), GSE62232 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62232) and GSE60753 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60753) were downloaded from the GEO database in NCBI. 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The mRNA and microRNA sequencing data were obtained from The Cancer Genome Atlas (https://tcga-data.nci.nih.gov).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM490987", "GSM490988", "GSM490989", "GSM490990", "GSM490991", "GSM490992", "GSM490993", "GSM490994", "GSM490995", "GSM490996", "GSM490997", "GSM490998", "GSM490999", "GSM491000", "GSM491001", "GSM491002", "GSM491003", "GSM491004", "GSM491005", "GSM491006"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Aberrant DNA methylation in hepatitis B and C virus-related hepatocellular carcinoma", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE60753", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60753", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE60753", "version": null, "note": "The sequencing datasets GSE19665 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19665), GSE62232 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62232) and GSE60753 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE60753) were downloaded from the GEO database in NCBI. 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