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pmid:34868228

Identification of Six Prognostic Genes in EGFR-Mutant Lung Adenocarcinoma Using Structure Network Algorithms.

Haomin Zhang · Di Lu · Qinglun Li · Fengfeng Lu · Jundong Zhang · Zining Wang · Xuechun Lu · Jinliang Wang

Frontiers in genetics · 2021 doi:10.3389/fgene.2021.755245

Paper

complete

Experiment

complete

Data

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Execution

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title
Identification of Six Prognostic Genes in EGFR-Mutant Lung Adenocarcinoma Using Structure Network Algorithms.
doi
10.3389/fgene.2021.755245
pmid
34868228
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[0]
Haomin Zhang
[1]
Di Lu
[2]
Qinglun Li
[3]
Fengfeng Lu
[4]
Jundong Zhang
[5]
Zining Wang
[6]
Xuechun Lu
[7]
Jinliang Wang
journal
Frontiers in genetics
year
2021
abstract
This study aims to determine hub genes related to the incidence and prognosis of EGFR-mutant (MT) lung adenocarcinoma (LUAD) with weighted gene coexpression network analysis (WGCNA). From The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we used 253 EGFR-MT LUAD samples and 38 normal lung tissue samples. At the same time, GSE19188 was additionally included to verify the accuracy of the predicted gene. To discover differentially expressed genes (DEGs), the R package "limma" was used. The R packages "WGCNA" and "survival" were used to perform WGCNA and survival analyses, respectively. The functional analysis was carried out with the R package "clusterProfiler." In total, 1450 EGFR-MT-specific DEGs were found, and 7 tumor-related modules were marked with WGCNA. We found 6 hub genes in DEGs that overlapped with the tumor-related modules, and the overexpression level of B3GNT3 was significantly associated with the worse OS (overall survival) of the EGFR-MT LUAD patients (p < 0.05). Functional analysis of the hub genes showed the metabolism and protein synthesis-related terms added value. In conclusion, we used WGCNA to identify hub genes in the development of EGFR-MT LUAD. The established prognostic factors could be used as clinical biomarkers. To confirm the mechanism of those genes in EGFR-MT LUAD, further molecular research is required.
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The TCGA-LUAD and GSE31210 gene expression data were built using a “WGCNA” package in the form of genetic co-expression modules in R (Zeng et al., 2016).
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sections[4] "Identification of Tumor-Related Modules With WGCNA" paragraph 2
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The TCGA-LUAD and GSE31210 gene expression data were built using a “WGCNA” package in the form of genetic co-expression modules in R (Zeng et al., 2016).
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Publicly available datasets were analyzed in this study. These data can be found here: GSE31210 GSE19188 https://portal.gdc.cancer.gov/.
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WGCNA identified seven tumor-related modules and six overlapping hub genes, with B3GNT3 overexpression significantly associated with worse overall survival in EGFR-mutant LUAD patients.
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We found 6 hub genes in DEGs that overlapped with the tumor-related modules, and the overexpression level of B3GNT3 was significantly associated with the worse OS (overall survival) of the EGFR-MT LUAD patients (p < 0.05).
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In total, 1450 EGFR-MT–specific DEGs were found, and 7 tumor-related modules were marked with WGCNA.
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We found 6 hub genes in DEGs that overlapped with the tumor-related modules, and the overexpression level of B3GNT3 was significantly associated with the worse OS (overall survival) of the EGFR-MT LUAD patients (p < 0.05).
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WGCNA identified seven tumor-related modules and six overlapping hub genes, with B3GNT3 overexpression significantly associated with worse overall survival in EGFR-mutant LUAD patients.
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method-2
family
clustering
specific
hierarchical
label
Clustering
dsl_operations array · 1 item
[0]
hierarchical_cluster
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
feature_matrix
evidence object · 3 fields
score
0.8
band
high
quote
dendrogram
[2] object · 10 fields
id
method-3
family
null
specific
null
label
Weighted gene co-expression network analysis (WGCNA)
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
The TCGA-LUAD and GSE31210 gene expression data were built using a “WGCNA” package in the form of genetic co-expression modules in R (Zeng et al., 2016).
targets array · 1 item
[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
differential_expression_fit
unit
p-value
tolerance
null
state
complete
note
The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold.
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 · 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 · 2 items
[0]
GSE31210
[1]
GSE19188
resolved_accessions array · 2 items
[0]
GSE31210
[1]
GSE19188
statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. These data can be found here: GSE31210 GSE19188 https://portal.gdc.cancer.gov/.
basis
The paper names GSE31210, GSE19188 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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 2 items
[0]
source:pmid:34868228
[1]
data:geo:GSE19188
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:GSE19188
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
2026-11-01T17:09:57Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
11572
completion_tokens
1687
cached_tokens
264
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:34868228
type
paper
label
pmid:34868228
[1] object · 3 fields
id
source:pmid:34868228
type
manuscript
label
PMID 34868228 full text
[2] object · 3 fields
id
data:geo:GSE19188
type
dataset
label
GEO GSE19188
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:34868228
type
paper
label
pmid:34868228
[1] object · 3 fields
id
source:pmid:34868228
type
manuscript
label
PMID 34868228 full text
[2] object · 3 fields
id
data:geo:GSE19188
type
dataset
label
GEO GSE19188
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34868228
type
extraction
used array · 1 item
[0]
source:pmid:34868228
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE19188
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE19188
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:34868228
parent_hash
sha256:0c29c1a7fe96de8f16895bbe05014e9a0d5f7b29091f7da3a3421caccb331d1f
fork_of
null
gaps array · 9 items
[0]
asset:data:geo:GSE19188 licence not read
[1]
asset:data:geo:GSE19188 not downloaded
[2]
asset:data:geo:GSE31210 licence not read
[3]
asset:data:geo:GSE31210 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
differential_expression
definition_version
f2132e96ae6c7a4e
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
limma
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:34868228", "kind": "science-record", "revision": 4, "content_hash": "sha256:8f3100088d1551573548c5f690885d6b3bcef685a68ef8f80a43b86b41bc6be2", "created_at": "2026-11-01T17:36:34Z", "updated_at": "2026-11-01T22:05:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Six Prognostic Genes in EGFR-Mutant Lung Adenocarcinoma Using Structure Network Algorithms.", "doi": "10.3389/fgene.2021.755245", "pmid": "34868228", "authors": ["Haomin Zhang", "Di Lu", "Qinglun Li", "Fengfeng Lu", "Jundong Zhang", "Zining Wang", "Xuechun Lu", "Jinliang Wang"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "This study aims to determine hub genes related to the incidence and prognosis of EGFR-mutant (MT) lung adenocarcinoma (LUAD) with weighted gene coexpression network analysis (WGCNA). From The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we used 253 EGFR-MT LUAD samples and 38 normal lung tissue samples. At the same time, GSE19188 was additionally included to verify the accuracy of the predicted gene. To discover differentially expressed genes (DEGs), the R package \"limma\" was used. The R packages \"WGCNA\" and \"survival\" were used to perform WGCNA and survival analyses, respectively. The functional analysis was carried out with the R package \"clusterProfiler.\" In total, 1450 EGFR-MT-specific DEGs were found, and 7 tumor-related modules were marked with WGCNA. We found 6 hub genes in DEGs that overlapped with the tumor-related modules, and the overexpression level of B3GNT3 was significantly associated with the worse OS (overall survival) of the EGFR-MT LUAD patients (p < 0.05). Functional analysis of the hub genes showed the metabolism and protein synthesis-related terms added value. In conclusion, we used WGCNA to identify hub genes in the development of EGFR-MT LUAD. The established prognostic factors could be used as clinical biomarkers. To confirm the mechanism of those genes in EGFR-MT LUAD, further molecular research is required.", "claims": [{"id": "claim-method", "statement": "The TCGA-LUAD and GSE31210 gene expression data were built using a “WGCNA” package in the form of genetic co-expression modules in R (Zeng et al., 2016).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34868228", "locator": "sections[4] \"Identification of Tumor-Related Modules With WGCNA\" paragraph 2", "quote": "The TCGA-LUAD and GSE31210 gene expression data were built using a “WGCNA” package in the form of genetic co-expression modules in R (Zeng et al., 2016)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found here: GSE31210 GSE19188 https://portal.gdc.cancer.gov/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34868228", "locator": "sections[15] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. These data can be found here: GSE31210 GSE19188 https://portal.gdc.cancer.gov/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "WGCNA identified seven tumor-related modules and six overlapping hub genes, with B3GNT3 overexpression significantly associated with worse overall survival in EGFR-mutant LUAD patients.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "We found 6 hub genes in DEGs that overlapped with the tumor-related modules, and the overexpression level of B3GNT3 was significantly associated with the worse OS (overall survival) of the EGFR-MT LUAD patients (p < 0.05)."}, "evidence": [{"asset": "source:pmid:34868228", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In total, 1450 EGFR-MT–specific DEGs were found, and 7 tumor-related modules were marked with WGCNA."}, {"asset": "source:pmid:34868228", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We found 6 hub genes in DEGs that overlapped with the tumor-related modules, and the overexpression level of B3GNT3 was significantly associated with the worse OS (overall survival) of the EGFR-MT LUAD patients (p < 0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "WGCNA identified seven tumor-related modules and six overlapping hub genes, with B3GNT3 overexpression significantly associated with worse overall survival in EGFR-mutant LUAD patients.", "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:34868228"], "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:GSE19188"], "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:GSE19188"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34868228", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.755245", "sha256": "sha256:4d7be83d1a93930b404c906bcfec61dd7e401624d421ad82694e3a4e28d91237", "bytes": 35385, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.755245", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8635158", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE19188", "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=GSE19188", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE19188", "version": null, "note": "Publicly available datasets were analyzed in this study. These data can be found here: GSE31210 GSE19188 https://portal.gdc.cancer.gov/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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