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pmid:39151107

Identification and Validation of Prognostic Model for Tumor Microenvironment-Associated Genes in Bladder Cancer Based on Single-Cell RNA Sequencing Data Sets.

Imran Safder · Henkel Valentine · Nicole Uzzo · John Sfakianos · Robert Uzzo · Shilpa Gupta · Jason Brown · Daniel Ranti · Elizabeth Plimack · George Haber · Christopher Weight · Alexander Kutikov · Philip Abbosh · Laura Bukavina

JCO precision oncology · 2024 doi:10.1200/PO.23.00661

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title
Identification and Validation of Prognostic Model for Tumor Microenvironment-Associated Genes in Bladder Cancer Based on Single-Cell RNA Sequencing Data Sets.
doi
10.1200/PO.23.00661
pmid
39151107
authors array · 14 items
[0]
Imran Safder
[1]
Henkel Valentine
[2]
Nicole Uzzo
[3]
John Sfakianos
[4]
Robert Uzzo
[5]
Shilpa Gupta
[6]
Jason Brown
[7]
Daniel Ranti
[8]
Elizabeth Plimack
[9]
George Haber
[10]
Christopher Weight
[11]
Alexander Kutikov
[12]
Philip Abbosh
[13]
Laura Bukavina
journal
JCO precision oncology
year
2024
abstract
PURPOSE: The purpose of this study was to elucidate the relationship between the tumor microenvironment (TME) and cellular diversity in bladder cancer (BLCA) progression, leveraging single-cell RNA sequencing (scRNA-seq) data to identify potential prognostic biomarkers and construct a prognostic model for BLCA. METHODS: We analyzed scRNA-seq data of normal and tumor bladder cells from the Gene Expression Omnibus (GEO) database to uncover crucial markers within the bladder TME. The study compared gene expression in normal versus tumor bladder cells, identifying differentially expressed genes. These genes were subsequently assessed for their prognostic significance using patient follow-up data from The Cancer Genome Atlas. Prognostic models were constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression analyses, focusing on eight genes of interest. The predictive performance of the model was also tested against additional GEO data sets (GSE31684, GSE13507, and GSE32894). RESULTS: The prognostic model demonstrated reliable prediction of patient outcomes. Validation through gene set enrichment analysis and immune cell infiltration assessment supported the model's efficacy. The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001). In the validation cohort, the AUC at 1, 2, and 3 years is 0.74, 0.74, and 0.72, respectively. CONCLUSION: Our findings proposed biomarkers with prognostic potential, laying the groundwork for future in vitro validation and therapeutic exploration. This contributes to a deeper understanding of the genes associated with bladder TME and may improve prognostic precision in BLCA management.
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To achieve this, we used step-wise Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression and multivariate Cox regression to identify survival-related DEGs and to develop a prognostic model.
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sections[4] "Construction of Prognostic Model Based on DEGs From scRNA-Seq Data" paragraph 2
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To achieve this, we used step-wise Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression and multivariate Cox regression to identify survival-related DEGs and to develop a prognostic model.
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sections[3] "Single-Cell RNA-Seq Data Set and Preprocessing" paragraph 2
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We obtained scRNA sequencing data for normal bladder cells from the Gene Expression Omnibus (GEO) database (data set GSE129845), complemented by tumor cell data courtesy of Dr Sfakianos' lab.
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The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001).
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The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001).
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The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001).
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The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001).
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Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer  
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sample_count
308
group_sizes
null
group_sizes_basis
null
platform
6947
taxon
Homo sapiens
title
A Molecular Taxonomy of Urothelial Carcinoma
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 8 items
[0]
asset:data:geo:GSE129845 not downloaded
[1]
asset:data:geo:GSE129845 licence not read
[2]
asset:data:geo:GSE13507 not downloaded
[3]
asset:data:geo:GSE13507 licence not read
[4]
asset:data:geo:GSE31684 not downloaded
[5]
asset:data:geo:GSE31684 licence not read
[6]
asset:data:geo:GSE32894 not downloaded
[7]
asset:data:geo:GSE32894 licence not read
analysis object · 4 fields
state
complete
methods array · 2 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
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verbatim
quote
To achieve this, we used step-wise Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression and multivariate Cox regression to identify survival-related DEGs and to develop a prognostic model.
[1] object · 10 fields
id
method-2
family
principal_component_analysis
specific
pca
label
Principal component analysis
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[0]
pca_fit
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parameters object · 0 fields
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[0]
wide_numeric_matrix
evidence object · 3 fields
score
0.8
band
high
quote
PCA
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[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
cox_ph
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per cent
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null
state
complete
note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
[1] object · 8 fields
id
target-published-estimate-hazard-ratio
claim_id
claim-target-result
operation
cox_ph
unit
hazard ratio
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 · 0 items
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]
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[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
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nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
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[0]
cox_ph
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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]
GSE129845
[1]
GSE31684
[2]
GSE13507
[3]
GSE32894
resolved_accessions array · 4 items
[0]
GSE129845
[1]
GSE31684
[2]
GSE13507
[3]
GSE32894
statements array · 1 item
[0]
We obtained scRNA sequencing data for normal bladder cells from the Gene Expression Omnibus (GEO) database (data set GSE129845), complemented by tumor cell data courtesy of Dr Sfakianos' lab.
basis
The paper names GSE129845, GSE31684, GSE13507, GSE32894 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
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[0]
cox_ph
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[0]
source:pmid:39151107
[1]
data:geo:GSE129845
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[0]
run_analysis
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[0]
data:geo:GSE129845
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review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
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MiniMax-M3.1-Flash
provider
minimax
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minimax
read_at
2026-11-01T19:28:50Z
independence
single_reader
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method
verbatim
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null
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5
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10632
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1833
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264
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[0] object · 4 fields
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extraction
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complete
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[2]
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not_run
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null
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[0]
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entities array · 3 items
[0] object · 3 fields
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pmid:39151107
type
paper
label
pmid:39151107
[1] object · 3 fields
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source:pmid:39151107
type
manuscript
label
PMID 39151107 full text
[2] object · 3 fields
id
data:geo:GSE129845
type
dataset
label
GEO GSE129845
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
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[0] object · 3 fields
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pmid:39151107
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paper
label
pmid:39151107
[1] object · 3 fields
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source:pmid:39151107
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manuscript
label
PMID 39151107 full text
[2] object · 3 fields
id
data:geo:GSE129845
type
dataset
label
GEO GSE129845
agent
agent:corpus-assay-engine
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id
activity-read-39151107
type
extraction
used array · 1 item
[0]
source:pmid:39151107
agent
agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE129845
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accession_resolution
used array · 1 item
[0]
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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agent:minimax-reader
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343fb30756ba6ec3
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2cb3e42f047d2ecf
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ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:39151107
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sha256:b1ba3105ef0828d09809e7eb61780b003062356e747892344ab816f407c529f8
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null
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[0]
asset:data:geo:GSE129845 licence not read
[1]
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[2]
asset:data:geo:GSE13507 licence not read
[3]
asset:data:geo:GSE13507 not downloaded
[4]
asset:data:geo:GSE31684 licence not read
[5]
asset:data:geo:GSE31684 not downloaded
[6]
asset:data:geo:GSE32894 licence not read
[7]
asset:data:geo:GSE32894 not downloaded
[8]
execution.not_run
[9]
review.human_critique
[10]
review.independent_reader
[11]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
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data_generation
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scrna_seq
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99e1195c7d6f
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unsupported
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99e1195c7d6f
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0.99
evidence array · 4 items
[0]
-Associated Genes in Bladder Cancer Based on Single-Cell RNA Sequencing Data Sets.
[1]
ladder cancer (BLCA) progression, leveraging single-cell RNA sequencing (scRNA-seq) data to identify potential progn
[2]
sion, leveraging single-cell RNA sequencing (scRNA-seq) data to identify potential prognostic bioma
[3]
gnostic model for BLCA. METHODS: We analyzed scRNA-seq data of normal and tumor bladder cells from
order_basis
paper_text_order:76
id
assay:1
[1] object · 11 fields
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data_generation
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rna_seq
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99e1195c7d6f
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assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 2 items
[0]
Genes in Bladder Cancer Based on Single-Cell RNA Sequencing Data Sets.
[1]
r (BLCA) progression, leveraging single-cell RNA sequencing (scRNA-seq) data to identify potential progn
order_basis
paper_text_order:88
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
survival_analysis
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f2132e96ae6c7a4e
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[0]
cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
To achieve this, we used step-wise Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression and multivariate Cox regression to identify survival-related DEGs and to develop a prognostic 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:39151107", "kind": "science-record", "revision": 2, "content_hash": "sha256:bd64270ac28f687df98081d6c99911a06bc64545bc42e6a938b5fd01a2898d2a", "created_at": "2026-11-01T20:29:16Z", "updated_at": "2026-11-01T21:33:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of Prognostic Model for Tumor Microenvironment-Associated Genes in Bladder Cancer Based on Single-Cell RNA Sequencing Data Sets.", "doi": "10.1200/PO.23.00661", "pmid": "39151107", "authors": ["Imran Safder", "Henkel Valentine", "Nicole Uzzo", "John Sfakianos", "Robert Uzzo", "Shilpa Gupta", "Jason Brown", "Daniel Ranti", "Elizabeth Plimack", "George Haber", "Christopher Weight", "Alexander Kutikov", "Philip Abbosh", "Laura Bukavina"], "journal": "JCO precision oncology", "year": 2024, "abstract": "PURPOSE: The purpose of this study was to elucidate the relationship between the tumor microenvironment (TME) and cellular diversity in bladder cancer (BLCA) progression, leveraging single-cell RNA sequencing (scRNA-seq) data to identify potential prognostic biomarkers and construct a prognostic model for BLCA.\nMETHODS: We analyzed scRNA-seq data of normal and tumor bladder cells from the Gene Expression Omnibus (GEO) database to uncover crucial markers within the bladder TME. The study compared gene expression in normal versus tumor bladder cells, identifying differentially expressed genes. These genes were subsequently assessed for their prognostic significance using patient follow-up data from The Cancer Genome Atlas. Prognostic models were constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression analyses, focusing on eight genes of interest. The predictive performance of the model was also tested against additional GEO data sets (GSE31684, GSE13507, and GSE32894).\nRESULTS: The prognostic model demonstrated reliable prediction of patient outcomes. Validation through gene set enrichment analysis and immune cell infiltration assessment supported the model's efficacy. The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001). In the validation cohort, the AUC at 1, 2, and 3 years is 0.74, 0.74, and 0.72, respectively.\nCONCLUSION: Our findings proposed biomarkers with prognostic potential, laying the groundwork for future in vitro validation and therapeutic exploration. This contributes to a deeper understanding of the genes associated with bladder TME and may improve prognostic precision in BLCA management.", "claims": [{"id": "claim-method", "statement": "To achieve this, we used step-wise Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression and multivariate Cox regression to identify survival-related DEGs and to develop a prognostic model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39151107", "locator": "sections[4] \"Construction of Prognostic Model Based on DEGs From scRNA-Seq Data\" paragraph 2", "quote": "To achieve this, we used step-wise Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression and multivariate Cox regression to identify survival-related DEGs and to develop a prognostic model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We obtained scRNA sequencing data for normal bladder cells from the Gene Expression Omnibus (GEO) database (data set GSE129845), complemented by tumor cell data courtesy of Dr Sfakianos' lab.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39151107", "locator": "sections[3] \"Single-Cell RNA-Seq Data Set and Preprocessing\" paragraph 2", "quote": "We obtained scRNA sequencing data for normal bladder cells from the Gene Expression Omnibus (GEO) database (data set GSE129845), complemented by tumor cell data courtesy of Dr Sfakianos' lab."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001)."}, "evidence": [{"asset": "source:pmid:39151107", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001).", "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:39151107"], "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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