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pmid:38652093

Identification of PPAR-related differentially expressed genes liver hepatocellular carcinoma and construction of a prognostic model based on data analysis and molecular docking.

Yumeng Wang · Shuqiang Li · Zihang Liu · Xuanzheng Li · Yifan Yu · Hao Liu

Journal of cellular and molecular medicine · 2024 doi:10.1111/jcmm.18304

Paper

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Experiment

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Data

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Analysis

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title
Identification of PPAR-related differentially expressed genes liver hepatocellular carcinoma and construction of a prognostic model based on data analysis and molecular docking.
doi
10.1111/jcmm.18304
pmid
38652093
authors array · 6 items
[0]
Yumeng Wang
[1]
Shuqiang Li
[2]
Zihang Liu
[3]
Xuanzheng Li
[4]
Yifan Yu
[5]
Hao Liu
journal
Journal of cellular and molecular medicine
year
2024
abstract
Liver hepatocellular carcinoma (LIHC) is a significant global health issue with limited treatment options. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the molecular mechanisms of LIHC development and identify potential targets for therapy. The expression of peroxisome proliferator-activated receptors (PPAR)-related genes was analysed in LIHC samples, and primary cell populations, including natural killer cells, T cells, B cells, myeloid cells, endothelial cells, fibroblasts and hepatocytes, were identified. Analysis of the differentially expressed genes (DEGs) between normal and tumour tissues revealed significant changes in gene expression in various cell populations. PPAR activity was evaluated using the 'AUCell' R software, which indicated higher scores in the normal versus the malignant hepatocytes. Furthermore, the DEGs showed significant enrichment of pathways related to lipid and glucose metabolism, cell development, differentiation and inflammation. A prognostic model was then constructed using 8 PPARs-related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator-Cox regression analysis, and validated in the TCGA-LIHC, ICGI-LIRI and GSE14520 datasets. Patients with low-risk scores had better prognosis in all cohorts. Based on the expression of the eight model genes, two clusters of patients were identified by ConsensusCluster analysis. We also predicted small-molecule drugs targeting the model genes, and identified perfluorohexanesulfonic acid, triflumizole and perfluorononanoic acid as potential candidates. Finally, wound healing assay confirmed that PPARD can promote the migration of liver cancer cells. Overall, our study offers novel perspectives on the molecular mechanisms of LIHC and potential areas for therapeutic intervention, which may facilitate the development of more effective treatment regimens.
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The prognostic PPARs‐related genes were screened by Least Absolute Shrinkage and Selection Operator (LASSO)‐Cox regression analysis using the ‘glmnet’ R package.
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sections[6] "Construction of the PPARs‐related gene signature and unsupervised clustering" paragraph 2
quote
The prognostic PPARs‐related genes were screened by Least Absolute Shrinkage and Selection Operator (LASSO)‐Cox regression analysis using the ‘glmnet’ R package.
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The datasets can be downloaded from the TCGA (https://portal.gdc.com), GEO (http://www.ncbi.nlm.nih.gov/geo/), and ICGC (https://icgc.org/) websites.
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sections[31] "DATA AVAILABILITY STATEMENT" paragraph 2
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The datasets can be downloaded from the TCGA (https://portal.gdc.com), GEO (http://www.ncbi.nlm.nih.gov/geo/), and ICGC (https://icgc.org/) websites.
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complete
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The study constructed and externally validated an eight-gene PPAR-related prognostic model for LIHC using LASSO-Cox regression analysis.
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sections[0] "Abstract" paragraph 1
quote
A prognostic model was then constructed using 8 PPARs‐related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator‐Cox regression analysis, and validated in the TCGA‐LIHC, ICGI‐LIRI and GSE14520 datasets.
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The study constructed and externally validated an eight-gene PPAR-related prognostic model for LIHC using LASSO-Cox regression analysis.
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[474]
GSM363449
[475]
GSM363450
[476]
GSM363451
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GSM712532
[478]
GSM712533
[479]
GSM712534
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GSM712535
[481]
GSM712536
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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:GSE149614
role
raw
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geo-series
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application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149614
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE149614
version
null
note
The datasets can be downloaded from the TCGA (https://portal.gdc.com), GEO (http://www.ncbi.nlm.nih.gov/geo/), and ICGC (https://icgc.org/) websites.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets can be downloaded from the TCGA (https://portal.gdc.com), GEO (http://www.ncbi.nlm.nih.gov/geo/), and ICGC (https://icgc.org/) websites.
access_statement_kind
data_availability_statement
sample_accessions array · 21 items
[0]
GSM4505944
[1]
GSM4505945
[2]
GSM4505946
[3]
GSM4505947
[4]
GSM4505948
[5]
GSM4505949
[6]
GSM4505950
[7]
GSM4505951
[8]
GSM4505952
[9]
GSM4505953
[10]
GSM4505954
[11]
GSM4505955
[12]
GSM4505956
[13]
GSM4505957
[14]
GSM4505958
[15]
GSM4505959
[16]
GSM4505960
[17]
GSM4505961
[18]
GSM4505962
[19]
GSM4505963
[20]
GSM4505964
sample_count
21
group_sizes
null
group_sizes_basis
null
platform
24676
taxon
Homo sapiens
title
A Single-Cell Atlas of the Multicellular Ecosystem of Primary and Metastatic Hepatocellular 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 · 4 items
[0]
asset:data:geo:GSE14520 not downloaded
[1]
asset:data:geo:GSE14520 licence not read
[2]
asset:data:geo:GSE149614 not downloaded
[3]
asset:data:geo:GSE149614 licence not read
analysis object · 4 fields
state
partial
methods array · 5 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 prognostic PPARs‐related genes were screened by Least Absolute Shrinkage and Selection Operator (LASSO)‐Cox regression analysis using the ‘glmnet’ R package.
[1] object · 10 fields
id
method-2
family
group_comparison
specific
wilcoxon
label
Group comparison
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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
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high
quote
Wilcoxon
[2] object · 10 fields
id
method-3
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
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count_matrix_with_condition
evidence object · 3 fields
score
0.8
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high
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limma
[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
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Pathway enrichment
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id
method-5
family
multi_omics_integration
specific
pathway_progeny
label
Multi-omics integration
dsl_operations array · 2 items
[0]
multiomics_factor_analysis
[1]
joint_pathway_score
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
aligned_multi_layer_matrices
evidence object · 3 fields
score
0.8
band
high
quote
PROGENy
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 · 2 items
[0]
GSE14520
[1]
GSE149614
resolved_accessions array · 2 items
[0]
GSE14520
[1]
GSE149614
statements array · 1 item
[0]
The datasets can be downloaded from the TCGA (https://portal.gdc.com), GEO (http://www.ncbi.nlm.nih.gov/geo/), and ICGC (https://icgc.org/) websites.
basis
The paper names GSE14520, GSE149614 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]
cox_ph
assets array · 2 items
[0]
source:pmid:38652093
[1]
data:geo:GSE14520
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
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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
2026-11-01T19:16:32Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
13252
completion_tokens
2235
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
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review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
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:38652093
type
paper
label
pmid:38652093
[1] object · 3 fields
id
source:pmid:38652093
type
manuscript
label
PMID 38652093 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:38652093
type
paper
label
pmid:38652093
[1] object · 3 fields
id
source:pmid:38652093
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manuscript
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PMID 38652093 full text
[2] object · 3 fields
id
data:geo:GSE14520
type
dataset
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GEO GSE14520
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-38652093
type
extraction
used array · 1 item
[0]
source:pmid:38652093
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agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE14520
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accession_resolution
used array · 1 item
[0]
data:geo:GSE14520
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agent:corpus-assay-engine
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[0] object · 3 fields
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agent:corpus-assay-engine
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software
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Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
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software
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MiniMax literature reader
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reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
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lineage object · 4 fields
parent_id
pmid:38652093
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sha256:ad92d7696532a9c2a39759d051421dbada3772ff945e928292620b9c85835e2d
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null
gaps array · 9 items
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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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assay_lexicon
99e1195c7d6f
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th limited treatment options. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the mo
[1]
. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the molecular mec
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paper_text_order:255
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assay:1
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data_generation
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rna_seq
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99e1195c7d6f
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paper_text_order:267
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hinese Academy of Sciences. HepG2 cells were cultured in minimum essential medium (MEM; Invitrogen; T
[1]
al bovine serum (FBS), while HUH7 cells were cultured in Dulbecco's modified Eagle's medium (DMEM; In
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human non‐small cell lung cancer cell lines HepG2 and HUH7 were purchased from the Cell Bank o
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f2132e96ae6c7a4e
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The prognostic PPARs‐related genes were screened by Least Absolute Shrinkage and Selection Operator (LASSO)‐Cox regression analysis using the ‘glmnet’ R package.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38652093", "kind": "science-record", "revision": 3, "content_hash": "sha256:1f6bf4ef313f9c71ace8688ead5806e7114f86a86a8ddc160c6ecfb73e013d1a", "created_at": "2026-11-01T19:20:37Z", "updated_at": "2026-11-01T22:11:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of PPAR-related differentially expressed genes liver hepatocellular carcinoma and construction of a prognostic model based on data analysis and molecular docking.", "doi": "10.1111/jcmm.18304", "pmid": "38652093", "authors": ["Yumeng Wang", "Shuqiang Li", "Zihang Liu", "Xuanzheng Li", "Yifan Yu", "Hao Liu"], "journal": "Journal of cellular and molecular medicine", "year": 2024, "abstract": "Liver hepatocellular carcinoma (LIHC) is a significant global health issue with limited treatment options. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the molecular mechanisms of LIHC development and identify potential targets for therapy. The expression of peroxisome proliferator-activated receptors (PPAR)-related genes was analysed in LIHC samples, and primary cell populations, including natural killer cells, T cells, B cells, myeloid cells, endothelial cells, fibroblasts and hepatocytes, were identified. Analysis of the differentially expressed genes (DEGs) between normal and tumour tissues revealed significant changes in gene expression in various cell populations. PPAR activity was evaluated using the 'AUCell' R software, which indicated higher scores in the normal versus the malignant hepatocytes. Furthermore, the DEGs showed significant enrichment of pathways related to lipid and glucose metabolism, cell development, differentiation and inflammation. A prognostic model was then constructed using 8 PPARs-related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator-Cox regression analysis, and validated in the TCGA-LIHC, ICGI-LIRI and GSE14520 datasets. Patients with low-risk scores had better prognosis in all cohorts. Based on the expression of the eight model genes, two clusters of patients were identified by ConsensusCluster analysis. We also predicted small-molecule drugs targeting the model genes, and identified perfluorohexanesulfonic acid, triflumizole and perfluorononanoic acid as potential candidates. Finally, wound healing assay confirmed that PPARD can promote the migration of liver cancer cells. Overall, our study offers novel perspectives on the molecular mechanisms of LIHC and potential areas for therapeutic intervention, which may facilitate the development of more effective treatment regimens.", "claims": [{"id": "claim-method", "statement": "The prognostic PPARs‐related genes were screened by Least Absolute Shrinkage and Selection Operator (LASSO)‐Cox regression analysis using the ‘glmnet’ R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38652093", "locator": "sections[6] \"Construction of the PPARs‐related gene signature and unsupervised clustering\" paragraph 2", "quote": "The prognostic PPARs‐related genes were screened by Least Absolute Shrinkage and Selection Operator (LASSO)‐Cox regression analysis using the ‘glmnet’ R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets can be downloaded from the TCGA (https://portal.gdc.com), GEO (http://www.ncbi.nlm.nih.gov/geo/), and ICGC (https://icgc.org/) websites.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38652093", "locator": "sections[31] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The datasets can be downloaded from the TCGA (https://portal.gdc.com), GEO (http://www.ncbi.nlm.nih.gov/geo/), and ICGC (https://icgc.org/) websites."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study constructed and externally validated an eight-gene PPAR-related prognostic model for LIHC using LASSO-Cox regression analysis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38652093", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A prognostic model was then constructed using 8 PPARs‐related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator‐Cox regression analysis, and validated in the TCGA‐LIHC, ICGI‐LIRI and GSE14520 datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study constructed and externally validated an eight-gene PPAR-related prognostic model for LIHC using LASSO-Cox regression analysis.", "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:38652093"], "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:38652093", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1111/jcmm.18304", "sha256": 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