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pmid:37857017

Identification and validation of a cancer-associated fibroblasts-related scoring system to predict prognosis and immune landscape in hepatocellular carcinoma through integrated analysis of single-cell and bulk RNA-sequencing.

Lingling Bao · Xuede Zhang · Wenjuan Wang · Bitao Jiang

Aging · 2023 doi:10.18632/aging.205099

Paper

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Experiment

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Data

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pmid:37857017
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title
Identification and validation of a cancer-associated fibroblasts-related scoring system to predict prognosis and immune landscape in hepatocellular carcinoma through integrated analysis of single-cell and bulk RNA-sequencing.
doi
10.18632/aging.205099
pmid
37857017
authors array · 4 items
[0]
Lingling Bao
[1]
Xuede Zhang
[2]
Wenjuan Wang
[3]
Bitao Jiang
journal
Aging
year
2023
abstract
BACKGROUND: Cancer-associated fibroblasts (CAFs) regulate the malignant biological behaviour of hepatocellular carcinoma (HCC) as a significant component of the tumour immune microenvironment (TIME). This study aimed to develop a CAFs-based scoring system to predict the prognosis and TIME of patients with HCC. METHODS: Data for the TCGA-LIHC and GSE14520 cohorts were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Single-cell RNA-sequencing data for HCC samples were retrieved from the GSE166635 cohort. The Least Absolute Shrinkage and Selection Operator algorithm was employed to develop a CAFs-related scoring system (CAFRss). The predictive value of the CAFRss was determined using Kaplan-Meier, Cox regression and Receiver Operating Characteristic curves. Additionally, the TIMER platform, single sample Gene Set Enrichment Analysis and the Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data algorithms were performed to determine the TIME landscape. Finally, the pRRophic algorithm was utilised for drug sensitivity analysis. RESULTS: The evaluation of the CAFRss system demonstrated its superior ability to predict the clinical outcome of patients with HCC. Additionally, CAFRss effectively distinguished HCC populations with distinct TIME landscapes. Furthermore, CAFRss-based risk stratification identified individuals with immune 'hot tumours' and predicted the survival of patients treated with ICBs. CONCLUSIONS: The developed CAFRss can serve as a predictive tool for determining the clinical outcome of HCC and differentiating populations with diverse TIME characteristics.
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The Least Absolute Shrinkage and Selection Operator algorithm was employed to develop a CAFs-related scoring system (CAFRss).
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The Least Absolute Shrinkage and Selection Operator algorithm was employed to develop a CAFs-related scoring system (CAFRss).
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The transcriptomic and clinical data for individuals with HCC were downloaded from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository) repository.
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sections[3] "Data collection" paragraph 2
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The transcriptomic and clinical data for individuals with HCC were downloaded from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository) repository.
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The CAFRss was an independent prognostic indicator for patients with HCC, with hazard ratios of 3.654 and 3.045 in univariate and multivariate Cox regression analyses, respectively.
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Uni- and multi-Cox regression analyses indicated that CAFRss was an independent prognostic indicator for patients with HCC, with hazard ratios of 3.654 (P < 0.001) and 3.045 (P < 0.001) (Figure 7A, 7B).
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sections[17] "Evaluation of the CAFRss" paragraph 2
quote
Uni- and multi-Cox regression analyses indicated that CAFRss was an independent prognostic indicator for patients with HCC, with hazard ratios of 3.654 (P < 0.001) and 3.045 (P < 0.001) (Figure 7A, 7B).
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The CAFRss was an independent prognostic indicator for patients with HCC, with hazard ratios of 3.654 and 3.045 in univariate and multivariate Cox regression analyses, respectively.
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[482]
GSM712537
[483]
GSM712538
[484]
GSM712539
[485]
GSM712540
[486]
GSM712541
[487]
GSM712542
sample_count
488
group_sizes
null
group_sizes_basis
null
platform
3921;571
taxon
Homo sapiens
title
Gene expression data of human hepatocellular carcinoma (HCC)
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[2] object · 15 fields
id
data:geo:GSE166635
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=GSE166635
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE166635
version
null
note
The transcriptomic and clinical data for individuals with HCC were downloaded from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository) repository.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The transcriptomic and clinical data for individuals with HCC were downloaded from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository) repository.
access_statement_kind
repository_route_statement
sample_accessions array · 2 items
[0]
GSM5076749
[1]
GSM5076750
sample_count
2
group_sizes
null
group_sizes_basis
null
platform
24676
taxon
Homo sapiens
title
TNFR2 HnRNPK-YAP Signaling Axis Promotes Primary Liver Cancer Development in Hepatic Progenitor Cells
resolution_checked_at
2026-11-01T18:46:34Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 4 items
[0]
asset:data:geo:GSE14520 not downloaded
[1]
asset:data:geo:GSE14520 licence not read
[2]
asset:data:geo:GSE166635 not downloaded
[3]
asset:data:geo:GSE166635 licence not read
analysis object · 4 fields
state
partial
methods array · 6 items
[0] object · 10 fields
id
method-1
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
0.7
band
medium
quote
Kaplan-Meier
[1] object · 10 fields
id
method-2
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
0.7
band
medium
quote
Cox regression
[2] object · 10 fields
id
method-3
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
[3] object · 10 fields
id
method-4
family
differential_expression
specific
limma_voom
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
limma
[4] object · 10 fields
id
method-5
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
[5] object · 10 fields
id
method-6
family
null
specific
null
label
LASSO regression algorithm
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 Least Absolute Shrinkage and Selection Operator algorithm was employed to develop a CAFs-related scoring system (CAFRss).
targets array · 1 item
[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
cox_ph
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 · 1 item
[0]
survival_km
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: kaplan_meier.
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]
GSE14520
[1]
GSE166635
resolved_accessions array · 2 items
[0]
GSE14520
[1]
GSE166635
statements array · 1 item
[0]
The transcriptomic and clinical data for individuals with HCC were downloaded from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository) repository.
basis
The paper names GSE14520, GSE166635 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 · 1 item
[0]
survival_km
assets array · 2 items
[0]
source:pmid:37857017
[1]
data:geo:GSE14520
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:GSE14520
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
2026-11-01T18:56:38Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
null
calls
5
usage object · 3 fields
prompt_tokens
12966
completion_tokens
3179
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:37857017
type
paper
label
pmid:37857017
[1] object · 3 fields
id
source:pmid:37857017
type
manuscript
label
PMID 37857017 full text
[2] object · 3 fields
id
data:geo:GSE14520
type
dataset
label
GEO GSE14520
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:37857017
type
paper
label
pmid:37857017
[1] object · 3 fields
id
source:pmid:37857017
type
manuscript
label
PMID 37857017 full text
[2] object · 3 fields
id
data:geo:GSE14520
type
dataset
label
GEO GSE14520
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-37857017
type
extraction
used array · 1 item
[0]
source:pmid:37857017
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE14520
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE14520
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:37857017
parent_hash
sha256:80c00553dcbbad3f697278548a3776873ac9fda03ef3c1afcf8735e45395fde9
fork_of
null
gaps array · 9 items
[0]
asset:data:geo:GSE14520 licence not read
[1]
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[2]
asset:data:geo:GSE166635 licence not read
[3]
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[4]
execution.not_run
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method.reader_named_unmapped
[6]
review.human_critique
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review.independent_reader
[8]
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assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_id
rna_seq
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99e1195c7d6f
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support_state
partial
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assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 3 items
[0]
integrated analysis of single-cell and bulk RNA-sequencing.
[1]
ne Expression Omnibus databases. Single-cell RNA-sequencing data for HCC samples were retrieved from the
[2]
o anti-tumour chemotherapeutic agents at the transcriptome expression level [26]. The IC50 values of di
order_basis
paper_text_order:166
id
assay:1
[1] object · 11 fields
role
data_generation
definition_id
methylation_array
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
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assay_lexicon
99e1195c7d6f
confidence
0.85
evidence array · 1 item
[0]
NTER, TIMER, CIBERSORT, XCELL, QUANTISEQ and EPIC), was used to estimate the level of immune c
order_basis
paper_text_order:2602
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assay:2
[2] object · 11 fields
role
analysis
definition_id
survival_analysis
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f2132e96ae6c7a4e
required_operations array · 1 item
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survival_km
support_state
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dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
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assay:3
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37857017", "kind": "science-record", "revision": 3, "content_hash": "sha256:ad4b57267dc7d420939ebfd3f1835728f5f5395cd43cc58a4e5efae998a808fb", "created_at": "2026-11-01T19:02:42Z", "updated_at": "2026-11-01T22:10:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of a cancer-associated fibroblasts-related scoring system to predict prognosis and immune landscape in hepatocellular carcinoma through integrated analysis of single-cell and bulk RNA-sequencing.", "doi": "10.18632/aging.205099", "pmid": "37857017", "authors": ["Lingling Bao", "Xuede Zhang", "Wenjuan Wang", "Bitao Jiang"], "journal": "Aging", "year": 2023, "abstract": "BACKGROUND: Cancer-associated fibroblasts (CAFs) regulate the malignant biological behaviour of hepatocellular carcinoma (HCC) as a significant component of the tumour immune microenvironment (TIME). This study aimed to develop a CAFs-based scoring system to predict the prognosis and TIME of patients with HCC.\nMETHODS: Data for the TCGA-LIHC and GSE14520 cohorts were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Single-cell RNA-sequencing data for HCC samples were retrieved from the GSE166635 cohort. The Least Absolute Shrinkage and Selection Operator algorithm was employed to develop a CAFs-related scoring system (CAFRss). The predictive value of the CAFRss was determined using Kaplan-Meier, Cox regression and Receiver Operating Characteristic curves. Additionally, the TIMER platform, single sample Gene Set Enrichment Analysis and the Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data algorithms were performed to determine the TIME landscape. Finally, the pRRophic algorithm was utilised for drug sensitivity analysis.\nRESULTS: The evaluation of the CAFRss system demonstrated its superior ability to predict the clinical outcome of patients with HCC. Additionally, CAFRss effectively distinguished HCC populations with distinct TIME landscapes. Furthermore, CAFRss-based risk stratification identified individuals with immune 'hot tumours' and predicted the survival of patients treated with ICBs.\nCONCLUSIONS: The developed CAFRss can serve as a predictive tool for determining the clinical outcome of HCC and differentiating populations with diverse TIME characteristics.", "claims": [{"id": "claim-method", "statement": "The Least Absolute Shrinkage and Selection Operator algorithm was employed to develop a CAFs-related scoring system (CAFRss).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37857017", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The Least Absolute Shrinkage and Selection Operator algorithm was employed to develop a CAFs-related scoring system (CAFRss)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The transcriptomic and clinical data for individuals with HCC were downloaded from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository) repository.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37857017", "locator": "sections[3] \"Data collection\" paragraph 2", "quote": "The transcriptomic and clinical data for individuals with HCC were downloaded from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/repository) repository."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The CAFRss was an independent prognostic indicator for patients with HCC, with hazard ratios of 3.654 and 3.045 in univariate and multivariate Cox regression analyses, respectively.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "Uni- and multi-Cox regression analyses indicated that CAFRss was an independent prognostic indicator for patients with HCC, with hazard ratios of 3.654 (P < 0.001) and 3.045 (P < 0.001) (Figure 7A, 7B)."}, "evidence": [{"asset": "source:pmid:37857017", "locator": "sections[17] \"Evaluation of the CAFRss\" paragraph 2", "quote": "Uni- and multi-Cox regression analyses indicated that CAFRss was an independent prognostic indicator for patients with HCC, with hazard ratios of 3.654 (P < 0.001) and 3.045 (P < 0.001) (Figure 7A, 7B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The CAFRss was an independent prognostic indicator for patients with HCC, with hazard ratios of 3.654 and 3.045 in univariate and multivariate Cox regression analyses, respectively.", "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:37857017"], "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:GSE14520"], "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:GSE14520"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37857017", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.205099", "sha256": "sha256:c54bb09b73e1ad05fc953b78a8e0f38f3b714d7b97380949b5fbe567e2272967", "bytes": 43485, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.18632/aging.205099", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10637792", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14520", "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=GSE14520", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14520", "version": null, "note": "The transcriptomic and clinical data for individuals with HCC were downloaded from The Cancer Genome Atlas (TCGA) 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