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pmid:34692847

Potential lncRNA Biomarkers for HBV-Related Hepatocellular Carcinoma Diagnosis Revealed by Analysis on Coexpression Network.

Shunqiang Nong · Xiaohao Chen · Zechen Wang · Guidan Xu · Wujun Wei · Bin Peng · Lü Zhou · Liuzhi Wei · Jingjie Zhao · Qiuju Wei · Yibin Deng · Lingzhang Meng

BioMed research international · 2021 doi:10.1155/2021/9972011

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Experiment

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Data

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Potential lncRNA Biomarkers for HBV-Related Hepatocellular Carcinoma Diagnosis Revealed by Analysis on Coexpression Network.
doi
10.1155/2021/9972011
pmid
34692847
authors array · 12 items
[0]
Shunqiang Nong
[1]
Xiaohao Chen
[2]
Zechen Wang
[3]
Guidan Xu
[4]
Wujun Wei
[5]
Bin Peng
[6]
Lü Zhou
[7]
Liuzhi Wei
[8]
Jingjie Zhao
[9]
Qiuju Wei
[10]
Yibin Deng
[11]
Lingzhang Meng
journal
BioMed research international
year
2021
abstract
BACKGROUND: Increasing evidence demonstrated that long noncoding RNA (lncRNA) could affect inflammatory tumor immune microenvironment by modulating gene expression and could be used as a biomarker for HBC-related hepatocellular carcinoma (HCC) but still needs further research. The aim of the present study was to determine an lncRNA signature for the diagnosis of HBV-related HCC. METHODS: HBV-related HCC expression profiles (GSE55092, GSE19665, and GSE84402) were abstracted from the GEO (Gene Expression Omnibus) data resource, and R package limma and RobustRankAggreg were employed to identify common differentially expressed genes (DEGs). Using machine learning, optimal diagnostic lncRNA molecular markers for HBV-related HCC were identified. The expression of candidate lncRNAs was cross-validated in GSE121248, and an ROC (receiver operating characteristic) curve of lncRNA biomarkers was carried out. Additionally, a coexpression network and functional annotation was built, after which a PPI (protein-protein interaction) network along with module analysis were conducted with the Cytoscape open source software. RESULT: A total of 38 DElncRNAs and 543 DEmRNAs were identified with a fold change larger than 2.0 and a P value < 0.05. By machine learning, AL356056.2, AL445524.1, TRIM52-AS1, AC093642.1, EHMT2-AS1, AC003991.1, AC008040.1, LINC00844, and LINC01018 were screened out as optional diagnostic lncRNA biosignatures for HBV-related HCC. The AUC (areas under the curve) of the SVM (support vector machine) model and random forest model were 0.957 and 0.904, respectively, and the specificity and sensitivity were 95.7 and 100% and 94.3 and 86.5%, respectively. The results of functional enrichment analysis showed that the integrated coexpressed DEmRNAs shared common cascades in the p53 signaling pathway, retinol metabolism, PI3K-Akt signaling cascade, and chemical carcinogenesis. The integrated DEmRNA PPI network complex was found to be comprised of 87 nodes, and two vital modules with a high degree were selected with the MCODE app. CONCLUSION: The present study identified nine potential diagnostic biomarkers for HBV-related HCC, all of which could potentially modulated gene expression related to inflammatory conditions in the tumor immune microenvironment. The functional annotation of the target DEmRNAs yielded novel evidence in evaluating the precise functions of lncRNA in HBV-related HCC.
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The DElncRNAs along with the DEmRNAs between HBV-linked HCC and nontumor tissues were computed through the limma R package V3.5.2 in R software in each dataset. Afterwards, the RobustRankAggreg (RRA) R package was used to integrate and analyze the three gene lists that were subsequently sorted via the logFC value.
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sections[4] "2.2. Screening for Differentially Expressed mRNAs and lncRNAs" paragraph 2
quote
The DElncRNAs along with the DEmRNAs between HBV-linked HCC and nontumor tissues were computed through the limma R package V3.5.2 in R software in each dataset.
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sections[4] "2.2. Screening for Differentially Expressed mRNAs and lncRNAs" paragraph 2
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Afterwards, the RobustRankAggreg (RRA) R package was used to integrate and analyze the three gene lists that were subsequently sorted via the logFC value.
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The datasets, as well as the code generated or analyzed in this work, can be accessed from the corresponding authors on reasonable request.
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The study identified nine potential diagnostic lncRNA biomarkers for HBV-related HCC.
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The present study identified nine potential diagnostic biomarkers for HBV-related HCC, all of which could potentially modulated gene expression related to inflammatory conditions in the tumor immune microenvironment.
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labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
medium
quote
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[2] object · 10 fields
id
method-3
family
machine_learning
specific
support_vector_machine
label
Machine learning
dsl_operations array · 3 items
[0]
train_classifier
[1]
cross_validate
[2]
roc_auc
missing_operations array · 0 items
parameters object · 1 field
auc
The AUC (areas under the curve)
data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
medium
quote
SVM
[3] object · 10 fields
id
method-4
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]
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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
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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 · 4 items
[0]
GSE55092
[1]
GSE19665
[2]
GSE84402
[3]
GSE121248
resolved_accessions array · 4 items
[0]
GSE55092
[1]
GSE19665
[2]
GSE84402
[3]
GSE121248
statements array · 1 item
[0]
The datasets, as well as the code generated or analyzed in this work, can be accessed from the corresponding authors on reasonable request.
basis
The paper names GSE55092, GSE19665, GSE84402, GSE121248 in NCBI-GEO data resource 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:34692847
[1]
data:geo:GSE121248
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:GSE121248
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
2026-11-01T17:04:56Z
independence
single_reader
evidence_check object · 2 fields
method
reordered
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
14391
completion_tokens
2108
cached_tokens
0
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
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minimax
gaps array · 3 items
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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:34692847
type
paper
label
pmid:34692847
[1] object · 3 fields
id
source:pmid:34692847
type
manuscript
label
PMID 34692847 full text
[2] object · 3 fields
id
data:geo:GSE121248
type
dataset
label
GEO GSE121248
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:34692847
type
paper
label
pmid:34692847
[1] object · 3 fields
id
source:pmid:34692847
type
manuscript
label
PMID 34692847 full text
[2] object · 3 fields
id
data:geo:GSE121248
type
dataset
label
GEO GSE121248
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34692847
type
extraction
used array · 1 item
[0]
source:pmid:34692847
agent
agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE121248
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE121248
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
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agent:corpus-assay-engine
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software
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Corpus assay engine
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id
agent:minimax-reader
type
software
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MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
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lineage object · 4 fields
parent_id
pmid:34692847
parent_hash
sha256:60ab9444623e59183faf9b7dfd9d033bde199d7af239bae3739abbef1f9c155b
fork_of
null
gaps array · 12 items
[0]
asset:data:geo:GSE121248 licence not read
[1]
asset:data:geo:GSE121248 not downloaded
[2]
asset:data:geo:GSE19665 licence not read
[3]
asset:data:geo:GSE19665 not downloaded
[4]
asset:data:geo:GSE55092 licence not read
[5]
asset:data:geo:GSE55092 not downloaded
[6]
asset:data:geo:GSE84402 licence not read
[7]
asset:data:geo:GSE84402 not downloaded
[8]
execution.not_run
[9]
review.human_critique
[10]
review.independent_reader
[11]
review.machine_critique
assays array · 1 item
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role
analysis
definition_id
differential_expression
definition_version
f2132e96ae6c7a4e
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[1]
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[2]
fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The DElncRNAs along with the DEmRNAs between HBV-linked HCC and nontumor tissues were computed through the limma R package V3.5.2 in R software in each dataset. Afterwards, the RobustRankAggreg (RRA) R package was used to integrate and analyze the three gene lists that were subsequently sorted via the logFC value.
order_basis
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34692847", "kind": "science-record", "revision": 5, "content_hash": "sha256:e7e5344d7348fee0153da76993353e3dc1d03b01051600726c1b8fc8401322c5", "created_at": "2026-11-01T17:36:22Z", "updated_at": "2026-11-01T22:47:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Potential lncRNA Biomarkers for HBV-Related Hepatocellular Carcinoma Diagnosis Revealed by Analysis on Coexpression Network.", "doi": "10.1155/2021/9972011", "pmid": "34692847", "authors": ["Shunqiang Nong", "Xiaohao Chen", "Zechen Wang", "Guidan Xu", "Wujun Wei", "Bin Peng", "Lü Zhou", "Liuzhi Wei", "Jingjie Zhao", "Qiuju Wei", "Yibin Deng", "Lingzhang Meng"], "journal": "BioMed research international", "year": 2021, "abstract": "BACKGROUND: Increasing evidence demonstrated that long noncoding RNA (lncRNA) could affect inflammatory tumor immune microenvironment by modulating gene expression and could be used as a biomarker for HBC-related hepatocellular carcinoma (HCC) but still needs further research. The aim of the present study was to determine an lncRNA signature for the diagnosis of HBV-related HCC.\nMETHODS: HBV-related HCC expression profiles (GSE55092, GSE19665, and GSE84402) were abstracted from the GEO (Gene Expression Omnibus) data resource, and R package limma and RobustRankAggreg were employed to identify common differentially expressed genes (DEGs). Using machine learning, optimal diagnostic lncRNA molecular markers for HBV-related HCC were identified. The expression of candidate lncRNAs was cross-validated in GSE121248, and an ROC (receiver operating characteristic) curve of lncRNA biomarkers was carried out. Additionally, a coexpression network and functional annotation was built, after which a PPI (protein-protein interaction) network along with module analysis were conducted with the Cytoscape open source software.\nRESULT: A total of 38 DElncRNAs and 543 DEmRNAs were identified with a fold change larger than 2.0 and a P value < 0.05. By machine learning, AL356056.2, AL445524.1, TRIM52-AS1, AC093642.1, EHMT2-AS1, AC003991.1, AC008040.1, LINC00844, and LINC01018 were screened out as optional diagnostic lncRNA biosignatures for HBV-related HCC. The AUC (areas under the curve) of the SVM (support vector machine) model and random forest model were 0.957 and 0.904, respectively, and the specificity and sensitivity were 95.7 and 100% and 94.3 and 86.5%, respectively. The results of functional enrichment analysis showed that the integrated coexpressed DEmRNAs shared common cascades in the p53 signaling pathway, retinol metabolism, PI3K-Akt signaling cascade, and chemical carcinogenesis. The integrated DEmRNA PPI network complex was found to be comprised of 87 nodes, and two vital modules with a high degree were selected with the MCODE app.\nCONCLUSION: The present study identified nine potential diagnostic biomarkers for HBV-related HCC, all of which could potentially modulated gene expression related to inflammatory conditions in the tumor immune microenvironment. The functional annotation of the target DEmRNAs yielded novel evidence in evaluating the precise functions of lncRNA in HBV-related HCC.", "claims": [{"id": "claim-method", "statement": "The DElncRNAs along with the DEmRNAs between HBV-linked HCC and nontumor tissues were computed through the limma R package V3.5.2 in R software in each dataset. Afterwards, the RobustRankAggreg (RRA) R package was used to integrate and analyze the three gene lists that were subsequently sorted via the logFC value.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34692847", "locator": "sections[4] \"2.2. Screening for Differentially Expressed mRNAs and lncRNAs\" paragraph 2", "quote": "The DElncRNAs along with the DEmRNAs between HBV-linked HCC and nontumor tissues were computed through the limma R package V3.5.2 in R software in each dataset."}, {"asset": "source:pmid:34692847", "locator": "sections[4] \"2.2. Screening for Differentially Expressed mRNAs and lncRNAs\" paragraph 2", "quote": "Afterwards, the RobustRankAggreg (RRA) R package was used to integrate and analyze the three gene lists that were subsequently sorted via the logFC value."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets, as well as the code generated or analyzed in this work, can be accessed from the corresponding authors on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34692847", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The datasets, as well as the code generated or analyzed in this work, can be accessed from the corresponding authors on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified nine potential diagnostic lncRNA biomarkers for HBV-related HCC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34692847", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The present study identified nine potential diagnostic biomarkers for HBV-related HCC, all of which could potentially modulated gene expression related to inflammatory conditions in the tumor immune microenvironment."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified nine potential diagnostic lncRNA biomarkers for HBV-related HCC.", "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:34692847"], "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:GSE121248"], "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:GSE121248"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34692847", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/9972011", "sha256": 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