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pmid:37534013

Prediction of prognosis and immunotherapy response in lung adenocarcinoma based on CD79A, DKK1 and VEGFC.

Qilong Zhang · Mingyuan Zhao · Shuangyan Lin · Qi Han · He Ye · Fang Peng · Li Li

Heliyon · 2023 doi:10.1016/j.heliyon.2023.e18503

Paper

complete

Experiment

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Data

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Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:37534013
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2026-11-01T19:02:18Z
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2026-11-01T22:10:00Z
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title
Prediction of prognosis and immunotherapy response in lung adenocarcinoma based on CD79A, DKK1 and VEGFC.
doi
10.1016/j.heliyon.2023.e18503
pmid
37534013
authors array · 7 items
[0]
Qilong Zhang
[1]
Mingyuan Zhao
[2]
Shuangyan Lin
[3]
Qi Han
[4]
He Ye
[5]
Fang Peng
[6]
Li Li
journal
Heliyon
year
2023
abstract
Background: Tumor immune microenvironment (TIME) is crucial for tumor initiation, progression, and metastasis; however, its relationship with lung adenocarcinoma (LUAD) is unknown. Traditional predictive models screen for biomarkers that are too general and infrequently associated with immune genes. Methods: RNA sequencing data of LUAD patients and immune-related gene sets were retrieved from public databases. Using the common genes shared by The Cancer Genome Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort), differential gene expression analysis, survival analysis, Lasso regression analysis, and univariate and multivariate Cox regression analyses were performed to generate a novel risk score model. LUAD cohort in International Cancer Genome Consortium (ICGC), GSE68465 cohort in Gene Expression Omnibus (GEO) and an immunohistochemical assay were used to validate the key genes constructed risk score. The LUAD-related prognosis, clinical indicators, immune infiltrate characteristics, response to immunotherapy, and response to chemotherapeutic agents in different risk groups were evaluated by CIBERSORT, ImmuCellAI, pRRophetic and other tools. Results: The risk score model was constructed using CD79a molecule (CD79A), Dickkopf WNT signaling pathway inhibitor 1 (DKK1), and vascular endothelial growth factor C (VEGFC). High risk score was identified as a negative predictor for overall survival (OS) in subgroup analyses with tumor stage, TNM classification, therapy outcome, and ESTIMATE scores (P < 0.05). Low risk score was positively associated with plasma cells, memory B cells, CD8 T cells, regulatory T cells and γδT cells (P < 0.05). In low-risk group, programmed cell death 1 receptor (PD1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and lymphocyte activating 3 (LAG3) and indoleamine 2,3-dioxygenase (IDO) were more robustly expressed (P < 0.05). The treatment responses of immune checkpoint blockade (ICB) therapy and chemotherapy were likewise superior in low-risk group (P < 0.05). In immunohistochemical analysis, the tumor group had significantly higher levels of CD79A, DKK1, and VEGFC than the adjacent normal group (P < 0.01). Conclusions: CD79A, DKK1 and VEGFC are important differential genes related to LUAD, risk score could reliably predict prognosis, composition of TIME and immunotherapy responses in LUAD patients. The excellent performance of the risk model shows its strong and broad application potential.
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The immune genes associated with prognosis were screened using the univariate Cox proportional hazards regression. To avoid overfitting, all genes were analyzed by the “glmnet” [22] package for Lasso regression analysis. After the Lasso model filtering, these genes were analyzed using the multivariable Cox proportional hazards regression to develop this immune-related risk score model.
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sections[4] "Establishment and verification of a risk score model for prognosis" paragraph 2
quote
The immune genes associated with prognosis were screened using the univariate Cox proportional hazards regression. To avoid overfitting, all genes were analyzed by the “glmnet” [22] package for Lasso regression analysis. After the Lasso model filtering, these genes were analyzed using the multivariable Cox proportional hazards regression to develop this immune-related risk score model.
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sections[26] "Data availability statement" paragraph 2
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methods array · 8 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
1
band
verbatim
quote
The immune genes associated with prognosis were screened using the univariate Cox proportional hazards regression. To avoid overfitting, all genes were analyzed by the “glmnet” [22] package for Lasso regression analysis. After the Lasso model filtering, these genes were analyzed using the multivariable Cox proportional hazards regression to develop this immune-related risk score model.
[1] object · 10 fields
id
method-2
family
group_comparison
specific
mann_whitney
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_mann_whitney
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
Mann-Whitney
[2] object · 10 fields
id
method-3
family
group_comparison
specific
wilcoxon
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
Wilcoxon
[3] object · 10 fields
id
method-4
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
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
Kaplan-Meier
[4] object · 10 fields
id
method-5
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
[5] object · 10 fields
id
method-6
family
differential_expression
specific
deseq2
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
0.8
band
high
quote
DESeq2
[6] object · 10 fields
id
method-7
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.8
band
high
quote
GO enrichment
[7] object · 10 fields
id
method-8
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
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
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 · 1 item
[0]
GSE68465
resolved_accessions array · 1 item
[0]
GSE68465
statements array · 1 item
[0]
Data will be made available on request.
basis
The paper names GSE68465 in Gene Expression Omnibus 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 · 2 items
[0]
source:pmid:37534013
[1]
data:geo:GSE68465
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:GSE68465
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
2026-11-01T18:48:39Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
12216
completion_tokens
1657
cached_tokens
256
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:37534013
type
paper
label
pmid:37534013
[1] object · 3 fields
id
source:pmid:37534013
type
manuscript
label
PMID 37534013 full text
[2] object · 3 fields
id
data:geo:GSE68465
type
dataset
label
GEO GSE68465
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:37534013
type
paper
label
pmid:37534013
[1] object · 3 fields
id
source:pmid:37534013
type
manuscript
label
PMID 37534013 full text
[2] object · 3 fields
id
data:geo:GSE68465
type
dataset
label
GEO GSE68465
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-37534013
type
extraction
used array · 1 item
[0]
source:pmid:37534013
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE68465
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accession_resolution
used array · 1 item
[0]
data:geo:GSE68465
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:37534013
parent_hash
sha256:2f5f60919550970d58b00304359dbca398727ed5fb3caab621e5a8beaa02b945
fork_of
null
gaps array · 7 items
[0]
asset:data:geo:GSE68465 licence not read
[1]
asset:data:geo:GSE68465 not downloaded
[2]
execution.not_run
[3]
method.reader_differs_from_extractor
[4]
review.human_critique
[5]
review.independent_reader
[6]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_id
rna_seq
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 2 items
[0]
ently associated with immune genes. Methods: RNA sequencing data of LUAD patients and immune-related gen
[1]
int inhibitor therapy was predicted by using RNA-Seq data and the ImmuCellAI network analysis pla
order_basis
paper_text_order:371
id
assay:1
[1] object · 11 fields
role
data_generation
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 4 items
[0]
hort in Gene Expression Omnibus (GEO) and an immunohistochemical assay were used to validate the key genes co
[1]
se superior in low-risk group (P < 0.05). In immunohistochemical analysis, the tumor group had significantly
[2]
KEGG pathways of immune-related DEGs.Fig. 2 Immunohistochemical analysis of CD79A, DKK1, and VEGFC CD79A, DK
[3]
resentative images of CD79A, DKK1, and VEGFC immunostaining in cancer tissues and paracancerous tissues
order_basis
paper_text_order:906
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assay:2
[2] object · 11 fields
role
analysis
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survival_analysis
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f2132e96ae6c7a4e
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[0]
cox_ph
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supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The immune genes associated with prognosis were screened using the univariate Cox proportional hazards regression. To avoid overfitting, all genes were analyzed by the “glmnet” [22] package for Lasso regression analysis. After the Lasso model filtering, these genes were analyzed using the multivariable Cox proportional hazards regression to develop this immune-related risk score model.
order_basis
consumes_earlier_output
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37534013", "kind": "science-record", "revision": 3, "content_hash": "sha256:235e4139ba93e253f357bfccc748e0ca535c4d83aba02d12e825993e015095c5", "created_at": "2026-11-01T19:02:18Z", "updated_at": "2026-11-01T22:10:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prediction of prognosis and immunotherapy response in lung adenocarcinoma based on CD79A, DKK1 and VEGFC.", "doi": "10.1016/j.heliyon.2023.e18503", "pmid": "37534013", "authors": ["Qilong Zhang", "Mingyuan Zhao", "Shuangyan Lin", "Qi Han", "He Ye", "Fang Peng", "Li Li"], "journal": "Heliyon", "year": 2023, "abstract": "Background: Tumor immune microenvironment (TIME) is crucial for tumor initiation, progression, and metastasis; however, its relationship with lung adenocarcinoma (LUAD) is unknown. Traditional predictive models screen for biomarkers that are too general and infrequently associated with immune genes.\nMethods: RNA sequencing data of LUAD patients and immune-related gene sets were retrieved from public databases. Using the common genes shared by The Cancer Genome Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort), differential gene expression analysis, survival analysis, Lasso regression analysis, and univariate and multivariate Cox regression analyses were performed to generate a novel risk score model. LUAD cohort in International Cancer Genome Consortium (ICGC), GSE68465 cohort in Gene Expression Omnibus (GEO) and an immunohistochemical assay were used to validate the key genes constructed risk score. The LUAD-related prognosis, clinical indicators, immune infiltrate characteristics, response to immunotherapy, and response to chemotherapeutic agents in different risk groups were evaluated by CIBERSORT, ImmuCellAI, pRRophetic and other tools.\nResults: The risk score model was constructed using CD79a molecule (CD79A), Dickkopf WNT signaling pathway inhibitor 1 (DKK1), and vascular endothelial growth factor C (VEGFC). High risk score was identified as a negative predictor for overall survival (OS) in subgroup analyses with tumor stage, TNM classification, therapy outcome, and ESTIMATE scores (P < 0.05). Low risk score was positively associated with plasma cells, memory B cells, CD8 T cells, regulatory T cells and γδT cells (P < 0.05). In low-risk group, programmed cell death 1 receptor (PD1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and lymphocyte activating 3 (LAG3) and indoleamine 2,3-dioxygenase (IDO) were more robustly expressed (P < 0.05). The treatment responses of immune checkpoint blockade (ICB) therapy and chemotherapy were likewise superior in low-risk group (P < 0.05). In immunohistochemical analysis, the tumor group had significantly higher levels of CD79A, DKK1, and VEGFC than the adjacent normal group (P < 0.01).\nConclusions: CD79A, DKK1 and VEGFC are important differential genes related to LUAD, risk score could reliably predict prognosis, composition of TIME and immunotherapy responses in LUAD patients. The excellent performance of the risk model shows its strong and broad application potential.", "claims": [{"id": "claim-method", "statement": "The immune genes associated with prognosis were screened using the univariate Cox proportional hazards regression. To avoid overfitting, all genes were analyzed by the “glmnet” [22] package for Lasso regression analysis. After the Lasso model filtering, these genes were analyzed using the multivariable Cox proportional hazards regression to develop this immune-related risk score model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37534013", "locator": "sections[4] \"Establishment and verification of a risk score model for prognosis\" paragraph 2", "quote": "The immune genes associated with prognosis were screened using the univariate Cox proportional hazards regression. To avoid overfitting, all genes were analyzed by the “glmnet” [22] package for Lasso regression analysis. After the Lasso model filtering, these genes were analyzed using the multivariable Cox proportional hazards regression to develop this immune-related risk score model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data will be made available on request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37534013", "locator": "sections[26] \"Data availability statement\" paragraph 2", "quote": "Data will be made available on request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:37534013"], "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:GSE68465"], "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:GSE68465"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37534013", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2023.e18503", "sha256": 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