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pmid:39697754

Integrative multi-omics and machine learning approach reveals tumor microenvironment-associated prognostic biomarkers in ovarian cancer.

Wenzhi Jiao · Shasha Yang · Yue Li · Yu Li · Shanshan Liu · Jianwei Shi · Minmin Yu

Translational cancer research · 2024 doi:10.21037/tcr-24-539

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title
Integrative multi-omics and machine learning approach reveals tumor microenvironment-associated prognostic biomarkers in ovarian cancer.
doi
10.21037/tcr-24-539
pmid
39697754
authors array · 7 items
[0]
Wenzhi Jiao
[1]
Shasha Yang
[2]
Yue Li
[3]
Yu Li
[4]
Shanshan Liu
[5]
Jianwei Shi
[6]
Minmin Yu
journal
Translational cancer research
year
2024
abstract
Background: Ovarian cancer (OC) is a globally prevalent malignancy with significant morbidity and mortality, yet its heterogeneity poses challenges in treatment and prognosis. Recognizing the crucial role of the tumor microenvironment (TME) in OC progression, this study leverages integrative multi-omics and machine learning to uncover TME-associated prognostic biomarkers, paving the way for more personalized therapeutic interventions. Methods: Employing a rigorous multi-omics approach, this study analyzed single-cell RNA sequencing (scRNA-seq) data from OC and normal tissue samples, including high-grade serous OC (HGSOC) from the Gene Expression Omnibus (GEO: GSE184880) and The Cancer Genome Atlas (TCGA) OC cohort, utilizing the Seurat package to annotate 700 TME-related genes. A prognostic model was developed using the least absolute shrinkage and selection operator (LASSO) regression and independently validated against similarly composed HGSOC datasets. Comprehensive gene expression and immune cell infiltration analyses were conducted, employing advanced algorithms like xCell to delineate the immune landscape of HGSOC. Results: Our investigation unveiled distinctive immune cell infiltration patterns and gene expression profiles within the TME of HGSOC. Notably, the prevalence of exhausted CD8+ T cells in high-risk patient samples emerged as a critical finding, underscoring the dualistic nature of the immune response in OC. The developed prognostic model, incorporating immune cell markers, exhibited robust predictive accuracy for patient outcomes, showing significant correlations with immunotherapy responses and drug sensitivities. Conclusions: This study presents a groundbreaking exploration of the OC TME, offering vital insights into its molecular intricacies. By systematically deciphering the TME-associated gene signatures, the research illuminates the potential of these biomarkers in refining patient prognosis and guiding treatment strategies. Our findings underscore the necessity for personalized medicine in OC treatment, potentially enhancing patient survival rates and quality of life. This study marks a significant stride in understanding and combatting the complexities of OC.
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To identify key genes influencing OC patient prognosis, we utilized the LASSO algorithm based on 700 TME-related genes in the training set. Subsequently, using stepwise multivariate COX regression analysis, we constructed a prognostic model for OC patients based on the key genes identified by LASSO.
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sections[10] "Construction of TME-related genes prognostic signature" paragraph 2
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To identify key genes influencing OC patient prognosis, we utilized the LASSO algorithm based on 700 TME-related genes in the training set. Subsequently, using stepwise multivariate COX regression analysis, we constructed a prognostic model for OC patients based on the key genes identified by LASSO.
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All processed and analyzed data, along with corresponding R code, will be made publicly available in a permanent repository, adhering to scientific standards of transparency and reproducibility.
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The prognostic model demonstrated an AUC of 0.57 at 1 year, 0.70 at 2 years, and 0.69 at 3 years.
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The prognostic model demonstrated an AUC of 0.57 at 1 year, 0.70 at 2 years, and 0.69 at 3 years.
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sections[20] "Development of a prognostic model based on key TME genes" paragraph 5
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The prognostic model demonstrated an AUC of 0.57 at 1 year, 0.70 at 2 years, and 0.69 at 3 years.
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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
correlation_analysis
specific
spearman
label
Correlation analysis
dsl_operations array · 1 item
[0]
spearman_rho
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
band
high
quote
Spearman correlation
[3] object · 10 fields
id
method-4
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
targets array · 1 item
[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
cox_ph
unit
auc
tolerance
null
state
complete
note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
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 · 2 items
[0]
GSE184880
[1]
GSE140082
resolved_accessions array · 2 items
[0]
GSE184880
[1]
GSE140082
statements array · 1 item
[0]
All processed and analyzed data, along with corresponding R code, will be made publicly available in a permanent repository, adhering to scientific standards of transparency and reproducibility.
basis
The paper names GSE184880, GSE140082 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:39697754
[1]
data:geo:GSE140082
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:GSE140082
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
2026-11-01T19:42:33Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
12408
completion_tokens
1498
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:39697754
type
paper
label
pmid:39697754
[1] object · 3 fields
id
source:pmid:39697754
type
manuscript
label
PMID 39697754 full text
[2] object · 3 fields
id
data:geo:GSE140082
type
dataset
label
GEO GSE140082
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:39697754
type
paper
label
pmid:39697754
[1] object · 3 fields
id
source:pmid:39697754
type
manuscript
label
PMID 39697754 full text
[2] object · 3 fields
id
data:geo:GSE140082
type
dataset
label
GEO GSE140082
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-39697754
type
extraction
used array · 1 item
[0]
source:pmid:39697754
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE140082
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE140082
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:39697754
parent_hash
sha256:abb3baf75a959ad4bb3b6d26c1a019e7a831ee4a9c0c72d8625382bf2f331735
fork_of
null
gaps array · 9 items
[0]
asset:data:geo:GSE140082 licence not read
[1]
asset:data:geo:GSE140082 not downloaded
[2]
asset:data:geo:GSE184880 licence not read
[3]
asset:data:geo:GSE184880 not downloaded
[4]
execution.not_run
[5]
method.reader_differs_from_extractor
[6]
review.human_critique
[7]
review.independent_reader
[8]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_id
scrna_seq
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
unsupported
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 4 items
[0]
us multi-omics approach, this study analyzed single-cell RNA sequencing (scRNA-seq) data from OC and normal tissue s
[1]
s study analyzed single-cell RNA sequencing (scRNA-seq) data from OC and normal tissue samples, inc
[2]
gration Using the Seurat package, individual scRNA-seq datasets were merged using the merge functio
[3]
SEA) T cells were extracted from the overall scRNA-seq dataset based on specific cell type annotati
order_basis
paper_text_order:603
id
assay:1
[1] object · 11 fields
role
data_generation
definition_id
rna_seq
definition_version
99e1195c7d6f
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support_state
partial
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assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
cs approach, this study analyzed single-cell RNA sequencing (scRNA-seq) data from OC and normal tissue s
order_basis
paper_text_order:615
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assay:2
[2] object · 11 fields
role
analysis
definition_id
survival_analysis
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f2132e96ae6c7a4e
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cox_ph
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supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
To identify key genes influencing OC patient prognosis, we utilized the LASSO algorithm based on 700 TME-related genes in the training set. Subsequently, using stepwise multivariate COX regression analysis, we constructed a prognostic model for OC patients based on the key genes identified by LASSO.
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:39697754", "kind": "science-record", "revision": 3, "content_hash": "sha256:639e7ec22d715dacf85dc5f9f62beaef5c1eff91737ac680c6f7f445018aa417", "created_at": "2026-11-01T20:30:01Z", "updated_at": "2026-11-01T22:13:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative multi-omics and machine learning approach reveals tumor microenvironment-associated prognostic biomarkers in ovarian cancer.", "doi": "10.21037/tcr-24-539", "pmid": "39697754", "authors": ["Wenzhi Jiao", "Shasha Yang", "Yue Li", "Yu Li", "Shanshan Liu", "Jianwei Shi", "Minmin Yu"], "journal": "Translational cancer research", "year": 2024, "abstract": "Background: Ovarian cancer (OC) is a globally prevalent malignancy with significant morbidity and mortality, yet its heterogeneity poses challenges in treatment and prognosis. Recognizing the crucial role of the tumor microenvironment (TME) in OC progression, this study leverages integrative multi-omics and machine learning to uncover TME-associated prognostic biomarkers, paving the way for more personalized therapeutic interventions.\nMethods: Employing a rigorous multi-omics approach, this study analyzed single-cell RNA sequencing (scRNA-seq) data from OC and normal tissue samples, including high-grade serous OC (HGSOC) from the Gene Expression Omnibus (GEO: GSE184880) and The Cancer Genome Atlas (TCGA) OC cohort, utilizing the Seurat package to annotate 700 TME-related genes. A prognostic model was developed using the least absolute shrinkage and selection operator (LASSO) regression and independently validated against similarly composed HGSOC datasets. Comprehensive gene expression and immune cell infiltration analyses were conducted, employing advanced algorithms like xCell to delineate the immune landscape of HGSOC.\nResults: Our investigation unveiled distinctive immune cell infiltration patterns and gene expression profiles within the TME of HGSOC. Notably, the prevalence of exhausted CD8+ T cells in high-risk patient samples emerged as a critical finding, underscoring the dualistic nature of the immune response in OC. The developed prognostic model, incorporating immune cell markers, exhibited robust predictive accuracy for patient outcomes, showing significant correlations with immunotherapy responses and drug sensitivities.\nConclusions: This study presents a groundbreaking exploration of the OC TME, offering vital insights into its molecular intricacies. By systematically deciphering the TME-associated gene signatures, the research illuminates the potential of these biomarkers in refining patient prognosis and guiding treatment strategies. Our findings underscore the necessity for personalized medicine in OC treatment, potentially enhancing patient survival rates and quality of life. This study marks a significant stride in understanding and combatting the complexities of OC.", "claims": [{"id": "claim-method", "statement": "To identify key genes influencing OC patient prognosis, we utilized the LASSO algorithm based on 700 TME-related genes in the training set. Subsequently, using stepwise multivariate COX regression analysis, we constructed a prognostic model for OC patients based on the key genes identified by LASSO.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39697754", "locator": "sections[10] \"Construction of TME-related genes prognostic signature\" paragraph 2", "quote": "To identify key genes influencing OC patient prognosis, we utilized the LASSO algorithm based on 700 TME-related genes in the training set. Subsequently, using stepwise multivariate COX regression analysis, we constructed a prognostic model for OC patients based on the key genes identified by LASSO."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All processed and analyzed data, along with corresponding R code, will be made publicly available in a permanent repository, adhering to scientific standards of transparency and reproducibility.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39697754", "locator": "sections[15] \"Data availability\" paragraph 2", "quote": "All processed and analyzed data, along with corresponding R code, will be made publicly available in a permanent repository, adhering to scientific standards of transparency and reproducibility."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The prognostic model demonstrated an AUC of 0.57 at 1 year, 0.70 at 2 years, and 0.69 at 3 years.", "kind": "quantitative", "target": {"value": 0.57, "unit": "auc", "tolerance": null, "source": "The prognostic model demonstrated an AUC of 0.57 at 1 year, 0.70 at 2 years, and 0.69 at 3 years."}, "evidence": [{"asset": "source:pmid:39697754", "locator": "sections[20] \"Development of a prognostic model based on key TME genes\" paragraph 5", "quote": "The prognostic model demonstrated an AUC of 0.57 at 1 year, 0.70 at 2 years, and 0.69 at 3 years."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The prognostic model demonstrated an AUC of 0.57 at 1 year, 0.70 at 2 years, and 0.69 at 3 years.", "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:39697754"], "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:GSE140082"], "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:GSE140082"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39697754", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tcr-24-539", "sha256": 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