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pmid:39744132

Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer.

Feizhi Lin · Xiaojiang Chen · Chengcai Liang · Ruopeng Zhang · Guoming Chen · Ziqi Zheng · Bowen Huang · Chengzhi Wei · Zhoukai Zhao · Feiyang Zhang · Zewei Chen · Shenghang Ruan · Yongming Chen · Runcong Nie · Yuangfang Li · Baiwei Zhao

Frontiers in pharmacology · 2024 doi:10.3389/fphar.2024.1477363

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Data

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Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer.
doi
10.3389/fphar.2024.1477363
pmid
39744132
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[0]
Feizhi Lin
[1]
Xiaojiang Chen
[2]
Chengcai Liang
[3]
Ruopeng Zhang
[4]
Guoming Chen
[5]
Ziqi Zheng
[6]
Bowen Huang
[7]
Chengzhi Wei
[8]
Zhoukai Zhao
[9]
Feiyang Zhang
[10]
Zewei Chen
[11]
Shenghang Ruan
[12]
Yongming Chen
[13]
Runcong Nie
[14]
Yuangfang Li
[15]
Baiwei Zhao
journal
Frontiers in pharmacology
year
2024
abstract
Aim: Programmed cell death (PCD) critically influences the tumor microenvironment (TME) and is intricately linked to tumor progression and patient prognosis. This study aimed to develop a novel prognostic indicator and marker of drug sensitivity in patients with gastric cancer (GC) based on PCD. Methods: We analyzed genes associated with 14 distinct PCD patterns using bulk transcriptome data and clinical information from TCGA-STAD for model construction with univariate Cox regression and LASSO regression analyses. Microarray data from GSE62254, GSE15459, and GSE26901 were used for validation. Single-cell transcriptome data from GSE183904 were analyzed to explore the relationship between TME and the newly constructed model, named PCD index (PCDI). Drug sensitivity comparisons were made between patients with high and low PCDI scores. Results: We developed a novel twelve-gene signature called PCDI. Upon validation, GC patients with higher PCDI scores had poorer prognoses. A high-performance nomogram integrating the PCDI with clinical features was also established. Additionally, single-cell transcriptome data analysis suggested that PCDI might be linked to critical components of the TME. Patients with high PCDI scores exhibited resistance to standard adjuvant chemotherapy and immunotherapy but might benefit from targeted treatments with NU7441, Dasatinib, and JQ1. Conclusion: The novel PCDI model shows significant potential in predicting clinical prognosis and drug sensitivity of GC, thereby facilitating personalized treatment strategies for patients with GC.
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Significant survival-related genes were identified using univariate Cox regression analysis (p < 0.05). LASSO (least absolute shrinkage and selection operator) regression, implemented through the “glmnet” package, was further employed to refine variables, thereby avoiding collinearity and overfitting (Engebretsen and Bohlin, 2019).
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Significant survival-related genes were identified using univariate Cox regression analysis (p < 0.05). LASSO (least absolute shrinkage and selection operator) regression, implemented through the “glmnet” package, was further employed to refine variables, thereby avoiding collinearity and overfitting (Engebretsen and Bohlin, 2019).
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Publicly available datasets were analyzed in this study. This data can be found here: TCGA: https://www.cancer.gov/ccg/research/genome-sequencing/tcga GEO: https://www.ncbi.nlm.nih.gov/geo/.
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Publicly available datasets were analyzed in this study. This data can be found here: TCGA: https://www.cancer.gov/ccg/research/genome-sequencing/tcga GEO: https://www.ncbi.nlm.nih.gov/geo/.
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[183]
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[184]
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[185]
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[189]
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[192]
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[194]
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[202]
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[203]
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[204]
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[205]
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[206]
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[299]
GSM1524072
sample_count
300
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study [gastric tumors]
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 8 items
[0]
asset:data:geo:GSE15459 not downloaded
[1]
asset:data:geo:GSE15459 licence not read
[2]
asset:data:geo:GSE183904 not downloaded
[3]
asset:data:geo:GSE183904 licence not read
[4]
asset:data:geo:GSE26901 not downloaded
[5]
asset:data:geo:GSE26901 licence not read
[6]
asset:data:geo:GSE62254 not downloaded
[7]
asset:data:geo:GSE62254 licence not read
analysis object · 4 fields
state
partial
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
Significant survival-related genes were identified using univariate Cox regression analysis (p < 0.05). LASSO (least absolute shrinkage and selection operator) regression, implemented through the “glmnet” package, was further employed to refine variables, thereby avoiding collinearity and overfitting (Engebretsen and Bohlin, 2019).
[1] object · 10 fields
id
method-2
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
[2] object · 10 fields
id
method-3
family
group_comparison
specific
anova
label
Group comparison
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[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
missing_operations array · 0 items
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
ANOVA
[3] object · 10 fields
id
method-4
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
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[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
principal_component_analysis
specific
pca
label
Principal component analysis
dsl_operations array · 1 item
[0]
pca_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
wide_numeric_matrix
evidence object · 3 fields
score
0.8
band
high
quote
Principal component analysis
[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
contingency_analysis
specific
chi_square
label
Categorical (contingency table) analysis
dsl_operations array · 1 item
[0]
chi_square_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
categorical_cross_tabulation
evidence object · 3 fields
score
0.8
band
high
quote
Chi-square
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 · 4 items
[0]
GSE62254
[1]
GSE15459
[2]
GSE26901
[3]
GSE183904
resolved_accessions array · 4 items
[0]
GSE62254
[1]
GSE15459
[2]
GSE26901
[3]
GSE183904
statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. This data can be found here: TCGA: https://www.cancer.gov/ccg/research/genome-sequencing/tcga GEO: https://www.ncbi.nlm.nih.gov/geo/.
basis
The paper names GSE62254, GSE15459, GSE26901, GSE183904 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 · 1 item
[0]
cox_ph
assets array · 2 items
[0]
source:pmid:39744132
[1]
data:geo:GSE15459
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:GSE15459
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
2026-11-01T19:43:56Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
17192
completion_tokens
2232
cached_tokens
256
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[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
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absent
status
not_run
mode
null
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:39744132
type
paper
label
pmid:39744132
[1] object · 3 fields
id
source:pmid:39744132
type
manuscript
label
PMID 39744132 full text
[2] object · 3 fields
id
data:geo:GSE15459
type
dataset
label
GEO GSE15459
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:39744132
type
paper
label
pmid:39744132
[1] object · 3 fields
id
source:pmid:39744132
type
manuscript
label
PMID 39744132 full text
[2] object · 3 fields
id
data:geo:GSE15459
type
dataset
label
GEO GSE15459
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agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-39744132
type
extraction
used array · 1 item
[0]
source:pmid:39744132
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE15459
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accession_resolution
used array · 1 item
[0]
data:geo:GSE15459
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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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
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snapshot_id
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lineage object · 4 fields
parent_id
pmid:39744132
parent_hash
sha256:ff53cdaf5e04f5647d3a967ada09efadd38caad2b91e75cb199a11c61e83640d
fork_of
null
gaps array · 13 items
[0]
asset:data:geo:GSE15459 licence not read
[1]
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[2]
asset:data:geo:GSE183904 licence not read
[3]
asset:data:geo:GSE183904 not downloaded
[4]
asset:data:geo:GSE26901 licence not read
[5]
asset:data:geo:GSE26901 not downloaded
[6]
asset:data:geo:GSE62254 licence not read
[7]
asset:data:geo:GSE62254 not downloaded
[8]
execution.not_run
[9]
method.reader_differs_from_extractor
[10]
review.human_critique
[11]
review.independent_reader
[12]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
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microarray
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
ox regression and LASSO regression analyses. Microarray data from GSE62254, GSE15459, and GSE26901 w
order_basis
paper_text_order:600
id
assay:1
[1] object · 11 fields
role
data_generation
definition_id
apoptosis_assay
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99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
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evidence array · 1 item
[0]
cluded in subsequent analyses, including 580 apoptosis genes, 52 pyroptosis genes, 87 ferroptosis g
order_basis
paper_text_order:3924
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
cox_ph
support_state
supported
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dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Significant survival-related genes were identified using univariate Cox regression analysis (p < 0.05). LASSO (least absolute shrinkage and selection operator) regression, implemented through the “glmnet” package, was further employed to refine variables, thereby avoiding collinearity and overfitting (Engebretsen and Bohlin, 2019).
order_basis
consumes_earlier_output
id
assay:3
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39744132", "kind": "science-record", "revision": 3, "content_hash": "sha256:23cc355da74b047d8f2e8cc2f1e53f4e4abc312fa9e99f4937899f2bdcd016db", "created_at": "2026-11-01T20:30:04Z", "updated_at": "2026-11-01T22:13:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer.", "doi": "10.3389/fphar.2024.1477363", "pmid": "39744132", "authors": ["Feizhi Lin", "Xiaojiang Chen", "Chengcai Liang", "Ruopeng Zhang", "Guoming Chen", "Ziqi Zheng", "Bowen Huang", "Chengzhi Wei", "Zhoukai Zhao", "Feiyang Zhang", "Zewei Chen", "Shenghang Ruan", "Yongming Chen", "Runcong Nie", "Yuangfang Li", "Baiwei Zhao"], "journal": "Frontiers in pharmacology", "year": 2024, "abstract": "Aim: Programmed cell death (PCD) critically influences the tumor microenvironment (TME) and is intricately linked to tumor progression and patient prognosis. This study aimed to develop a novel prognostic indicator and marker of drug sensitivity in patients with gastric cancer (GC) based on PCD.\nMethods: We analyzed genes associated with 14 distinct PCD patterns using bulk transcriptome data and clinical information from TCGA-STAD for model construction with univariate Cox regression and LASSO regression analyses. Microarray data from GSE62254, GSE15459, and GSE26901 were used for validation. Single-cell transcriptome data from GSE183904 were analyzed to explore the relationship between TME and the newly constructed model, named PCD index (PCDI). Drug sensitivity comparisons were made between patients with high and low PCDI scores.\nResults: We developed a novel twelve-gene signature called PCDI. Upon validation, GC patients with higher PCDI scores had poorer prognoses. A high-performance nomogram integrating the PCDI with clinical features was also established. Additionally, single-cell transcriptome data analysis suggested that PCDI might be linked to critical components of the TME. Patients with high PCDI scores exhibited resistance to standard adjuvant chemotherapy and immunotherapy but might benefit from targeted treatments with NU7441, Dasatinib, and JQ1.\nConclusion: The novel PCDI model shows significant potential in predicting clinical prognosis and drug sensitivity of GC, thereby facilitating personalized treatment strategies for patients with GC.", "claims": [{"id": "claim-method", "statement": "Significant survival-related genes were identified using univariate Cox regression analysis (p < 0.05). LASSO (least absolute shrinkage and selection operator) regression, implemented through the “glmnet” package, was further employed to refine variables, thereby avoiding collinearity and overfitting (Engebretsen and Bohlin, 2019).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39744132", "locator": "sections[5] \"2.3 Prognostic gene signature development for GC patients\" paragraph 2", "quote": "Significant survival-related genes were identified using univariate Cox regression analysis (p < 0.05). LASSO (least absolute shrinkage and selection operator) regression, implemented through the “glmnet” package, was further employed to refine variables, thereby avoiding collinearity and overfitting (Engebretsen and Bohlin, 2019)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA: https://www.cancer.gov/ccg/research/genome-sequencing/tcga GEO: https://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39744132", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA: https://www.cancer.gov/ccg/research/genome-sequencing/tcga GEO: https://www.ncbi.nlm.nih.gov/geo/."}], "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:39744132"], "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:GSE15459"], "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:GSE15459"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39744132", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2024.1477363", "sha256": "sha256:47b2be9bd5f65b8a3c96ba234cfb01ac8b8ec4b56c506eacc9ae8c3967057c2e", "bytes": 57977, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2024.1477363", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11688280", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE15459", "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=GSE15459", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE15459", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA: https://www.cancer.gov/ccg/research/genome-sequencing/tcga GEO: https://www.ncbi.nlm.nih.gov/geo/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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