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pmid:34147096

Screening the genome for HCC-specific CpG methylation signatures as biomarkers for diagnosis and prognosis evaluation.

Rui-Kun Zhang · Jia-Lin Liu

BMC medical genomics · 2021 doi:10.1186/s12920-021-01015-9

Paper

complete

Experiment

complete

Data

partial

Analysis

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absent

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pmid:34147096
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title
Screening the genome for HCC-specific CpG methylation signatures as biomarkers for diagnosis and prognosis evaluation.
doi
10.1186/s12920-021-01015-9
pmid
34147096
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[0]
Rui-Kun Zhang
[1]
Jia-Lin Liu
journal
BMC medical genomics
year
2021
abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and invasive malignant tumors in the world. The change in DNA methylation is a key event in HCC. METHODS: Methylation datasets for HCC and 17 other types of cancer were downloaded from The Cancer Genome Atlas (TCGA). The CpG sites with large differences in methylation between tumor tissues and paracancerous tissues were identified. We used the HCC methylation dataset downloaded from the TCGA as the training set and removed the overlapping sites among all cancer datasets to ensure that only CpG sites specific to HCC remained. Logistic regression analysis was performed to select specific biomarkers that can be used to diagnose HCC, and two datasets-GSE157341 and GSE54503-downloaded from GEO as validation sets were used to validate our model. We also used a Cox regression model to select CpG sites related to patient prognosis. RESULTS: We identified 6 HCC-specific methylated CpG sites as biomarkers for HCC diagnosis. In the training set, the area under the receiver operating characteristic (ROC) curve (AUC) for the model containing all these sites was 0.971. The AUCs were 0.8802 and 0.9711 for the two validation sets from the GEO database. In addition, 3 other CpG sites were analyzed and used to create a risk scoring model for patient prognosis and survival prediction. CONCLUSIONS: Through the analysis of HCC methylation datasets from the TCGA and Gene Expression Omnibus (GEO) databases, potential biomarkers for HCC diagnosis and prognosis evaluation were ascertained.
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Student’s t test was applied to compares the difference between the two groups.
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TCGA: https://tcga-data.nci.nih.gov, now hosted at GDC: https:// portal.gdc.cancer.gov/. GSE157341: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157341. GSE54503: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54503
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Detailed information on HCC-specific CpG sites
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[4]
95% CI for the Coefficient
[5]
p value
[1] array · 6 items
[0]
cg26581504
[1]
BCO2
[2]
3507.98
[3]
8.162797
[4]
5.40 to 11.67
[5]
2.31 × 10–7
[2] array · 6 items
[0]
cg05106294
[1]
DKK3
[2]
689.79
[3]
6.536393
[4]
2.76 to11.30
[5]
2.42 × 10–3
[3] array · 6 items
[0]
cg20342184
[1]
GRHL2
[2]
60.14
[3]
4.096723
[4]
0.29 to 8.81
[5]
5.59 × 10–2
[4] array · 6 items
[0]
cg23623667
[1]
KCNQ1
[2]
149.58
[3]
5.00
[4]
1.03 to 9.79
[5]
2.22 × 10–2
[5] array · 6 items
[0]
cg14250130
[1]
PFKP
[2]
0.001
[3]
− 6.51
[4]
(− 11.20) to (− 2.15)
[5]
3.87 × 10–3
[6] array · 6 items
[0]
cg13564825
[1]
PPP1R14A
[2]
141.75
[3]
4.95
[4]
1.64 to 8.99
[5]
7.09 × 10–3
locator
section[8]/table-wrap[1]#Tab1
[4] object · 16 fields
id
asset:table:pmid:34147096:2
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:4393f142b53b3c3f6267a8039ef636dc00a7c8e6082400c926864aff02feaf71
bytes
451
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[10]/table-wrap[1]#Tab2
version
null
note
CpG sites related to patient survival
structure object · 5 fields
pmcid
PMC8214801
section_index
10
section_title
Selecting the prognostic HCC-specific sites
row_count
4
column_count
6
table object · 8 fields
label
Table 2
caption
CpG sites related to patient survival
rows array · 4 items
[0] array · 6 items
[0]
ID
[1]
Gene symbol
[2]
HR
[3]
Coefficient
[4]
95% CI for the HR
[5]
p value
[1] array · 6 items
[0]
cg08167706
[1]
AKR1B1
[2]
0.392
[3]
− 0.935
[4]
0.156–0.981
[5]
0.045
[2] array · 6 items
[0]
cg03757145
[1]
CDKL2
[2]
3.672
[3]
1.300
[4]
1.051–12.832
[5]
0.041
[3] array · 6 items
[0]
cg09626894
[1]
CFTR
[2]
2.952
[3]
1.082
[4]
1.051–8.291
[5]
0.039
locator
section[10]/table-wrap[1]#Tab2
gaps array · 4 items
[0]
asset:data:geo:GSE157341 not downloaded
[1]
asset:data:geo:GSE157341 licence not read
[2]
asset:data:geo:GSE54503 not downloaded
[3]
asset:data:geo:GSE54503 licence not read
analysis object · 4 fields
state
partial
methods array · 5 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
band
medium
quote
Cox regression
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[0]
logrank_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
log-rank
[2] object · 10 fields
id
method-3
family
regression_modelling
specific
logistic
label
Regression modelling
dsl_operations array · 1 item
[0]
glm_logit_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
predictors_and_outcome
evidence object · 3 fields
score
0.7
band
medium
quote
Logistic regression
[3] object · 10 fields
id
method-4
family
diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
[1]
roc_curve
[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.8
band
high
quote
ROC curve
[4] object · 10 fields
id
method-5
family
null
specific
null
label
Student’s t test
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
band
verbatim
quote
Student’s t test was applied to compares the difference between the two groups.
targets array · 0 items
gaps array · 1 item
[0]
method.reader_named_unmapped
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 · 1 item
[0]
cox_ph
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: cox_proportional_hazards.
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 · 2 items
[0]
GSE157341
[1]
GSE54503
resolved_accessions array · 2 items
[0]
GSE157341
[1]
GSE54503
statements array · 1 item
[0]
TCGA: https://tcga-data.nci.nih.gov, now hosted at GDC: https:// portal.gdc.cancer.gov/. GSE157341: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157341. GSE54503: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54503
basis
The paper names GSE157341, GSE54503 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
cox_ph
assets array · 4 items
[0]
source:pmid:34147096
[1]
data:geo:GSE157341
[2]
asset:table:pmid:34147096:1
[3]
asset:table:pmid:34147096:2
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:GSE157341
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
2026-10-31T18:31:08Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
31638
completion_tokens
1908
cached_tokens
776
stages array · 1 item
[0] object · 4 fields
id
extraction
state
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
mode
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:34147096
type
paper
label
pmid:34147096
[1] object · 3 fields
id
source:pmid:34147096
type
manuscript
label
PMID 34147096 full text
[2] object · 3 fields
id
data:geo:GSE157341
type
dataset
label
GEO GSE157341
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:34147096
type
paper
label
pmid:34147096
[1] object · 3 fields
id
source:pmid:34147096
type
manuscript
label
PMID 34147096 full text
[2] object · 3 fields
id
data:geo:GSE157341
type
dataset
label
GEO GSE157341
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34147096
type
extraction
used array · 1 item
[0]
source:pmid:34147096
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE157341
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE157341
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
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:34147096
parent_hash
sha256:aaf30f55a8c9989ddb22f22fb31c9dcca657b8bc5280414edcf2fd8c5d9e1361
fork_of
null
gaps array · 9 items
[0]
asset:data:geo:GSE157341 licence not read
[1]
asset:data:geo:GSE157341 not downloaded
[2]
asset:data:geo:GSE54503 licence not read
[3]
asset:data:geo:GSE54503 not downloaded
[4]
execution.not_run
[5]
method.reader_named_unmapped
[6]
review.human_critique
[7]
review.independent_reader
[8]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Cox regression
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34147096", "kind": "science-record", "revision": 7, "content_hash": "sha256:b9f62637cf3408dbe2d65decd36d32e2886940a40a8d55d7a0517f088d198a99", "created_at": "2026-11-01T15:41:39Z", "updated_at": "2026-11-01T22:04:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Screening the genome for HCC-specific CpG methylation signatures as biomarkers for diagnosis and prognosis evaluation.", "doi": "10.1186/s12920-021-01015-9", "pmid": "34147096", "authors": ["Rui-Kun Zhang", "Jia-Lin Liu"], "journal": "BMC medical genomics", "year": 2021, "abstract": "BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and invasive malignant tumors in the world. The change in DNA methylation is a key event in HCC.\nMETHODS: Methylation datasets for HCC and 17 other types of cancer were downloaded from The Cancer Genome Atlas (TCGA). The CpG sites with large differences in methylation between tumor tissues and paracancerous tissues were identified. We used the HCC methylation dataset downloaded from the TCGA as the training set and removed the overlapping sites among all cancer datasets to ensure that only CpG sites specific to HCC remained. Logistic regression analysis was performed to select specific biomarkers that can be used to diagnose HCC, and two datasets-GSE157341 and GSE54503-downloaded from GEO as validation sets were used to validate our model. We also used a Cox regression model to select CpG sites related to patient prognosis.\nRESULTS: We identified 6 HCC-specific methylated CpG sites as biomarkers for HCC diagnosis. In the training set, the area under the receiver operating characteristic (ROC) curve (AUC) for the model containing all these sites was 0.971. The AUCs were 0.8802 and 0.9711 for the two validation sets from the GEO database. In addition, 3 other CpG sites were analyzed and used to create a risk scoring model for patient prognosis and survival prediction.\nCONCLUSIONS: Through the analysis of HCC methylation datasets from the TCGA and Gene Expression Omnibus (GEO) databases, potential biomarkers for HCC diagnosis and prognosis evaluation were ascertained.", "claims": [{"id": "claim-method", "statement": "Student’s t test was applied to compares the difference between the two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34147096", "locator": "sections[5] \"DNA differential methylation analysis\" paragraph 2", "quote": "Student’s t test was applied to compares the difference between the two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "TCGA: https://tcga-data.nci.nih.gov, now hosted at GDC: https:// portal.gdc.cancer.gov/. GSE157341: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157341. GSE54503: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54503", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34147096", "locator": "sections[22] \"Availability of data and materials\" paragraph 2", "quote": "TCGA: https://tcga-data.nci.nih.gov, now hosted at GDC: https:// portal.gdc.cancer.gov/. GSE157341: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157341. GSE54503: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54503"}], "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:34147096"], "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. 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