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pmid:36860731

Development of Prognostic Features of Hepatocellular Carcinoma Based on Metabolic Gene Classification and Immune and Oxidative Stress Characteristic Analysis.

Shimeng Cui · Minghao Zhang · Shanshan Bai · Yanfang Bi · Shan Cong · Shi Jin · Shuang Li · Hui He · Jian Zhang

Oxidative medicine and cellular longevity · 2023 doi:10.1155/2023/1847700

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Experiment

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pmid:36860731
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2026-11-01T19:01:29Z
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title
Development of Prognostic Features of Hepatocellular Carcinoma Based on Metabolic Gene Classification and Immune and Oxidative Stress Characteristic Analysis.
doi
10.1155/2023/1847700
pmid
36860731
authors array · 9 items
[0]
Shimeng Cui
[1]
Minghao Zhang
[2]
Shanshan Bai
[3]
Yanfang Bi
[4]
Shan Cong
[5]
Shi Jin
[6]
Shuang Li
[7]
Hui He
[8]
Jian Zhang
journal
Oxidative medicine and cellular longevity
year
2023
abstract
Background: The molecular classification of HCC premised on metabolic genes might give assistance for diagnosis, therapy, prognosis prediction, immune infiltration, and oxidative stress in addition to supplementing the limitations of the clinical staging system. This would help to better represent the deeper features of HCC. Methods: TCGA datasets combined with GSE14520 and HCCDB18 datasets were used to determine the metabolic subtype (MC) using ConsensusClusterPlus. ssGSEA method was used to calculate the IFNγ score, the oxidative stress pathway scores, and the score distribution of 22 distinct immune cells, and their differential expressions were assessed with the use of CIBERSORT. To generate a subtype classification feature index, LDA was utilized. Screening of the metabolic gene coexpression modules was done with the help of WGCNA. Results: Three MCs (MC1, MC2, and MC3) were identified and showed different prognoses (MC2-poor and MC1-better). Although MC2 had a high immune microenvironment infiltration, T cell exhaustion markers were expressed at a high level in MC2 in contrast with MC1. Most oxidative stress-related pathways are inhibited in the MC2 subtype and activated in the MC1 subtype. The immunophenotyping of pan-cancer showed that the C1 and C2 subtypes with poor prognosis accounted for significantly higher proportions of MC2 and MC3 subtypes than MC1, while the better prognostic C3 subtype accounted for significantly lower proportions of MC2 than MC1. As per the findings of the TIDE analysis, MC1 had a greater likelihood of benefiting from immunotherapeutic regimens. MC2 was found to have a greater sensitivity to traditional chemotherapy drugs. Finally, 7 potential gene markers indicate HCC prognosis. Conclusion: The difference (variation) in tumor microenvironment and oxidative stress among metabolic subtypes of HCC was compared from multiple angles and levels. A complete and thorough clarification of the molecular pathological properties of HCC, the exploration of reliable markers for diagnosis, the improvement of the cancer staging system, and the guiding of individualized treatment of HCC all gain benefit greatly from molecular classification associated with metabolism.
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We employed the ssGSEA approach to determine each patient's IFNγ score to assess the Th1/IFNγ expression variations in metabolic subtypes and enrichment score of 14 oxidative stress-related biological pathways.
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sections[6] "2.4. Single-Sample Gene Set Enrichment Analysis (ssGSEA)" paragraph 2
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We employed the ssGSEA approach to determine each patient's IFNγ score to assess the Th1/IFNγ expression variations in metabolic subtypes and enrichment score of 14 oxidative stress-related biological pathways.
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The datasets analyzed in this study could be found in GSE14520 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14520, in GSE91061 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE91061, and in GSE14502 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14502.
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sections[25] "Data Availability" paragraph 2
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The datasets analyzed in this study could be found in GSE14520 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14520, in GSE91061 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE91061, and in GSE14502 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14502.
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Three metabolic HCC subtypes were identified, with MC2 having an unfavorable prognosis and MC1 having a favorable prognosis.
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Three MCs (MC1, MC2, and MC3) were identified and showed different prognoses (MC2-poor and MC1-better).
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Three metabolic HCC subtypes were identified, with MC2 having an unfavorable prognosis and MC1 having a favorable prognosis.
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488
group_sizes
null
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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
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[3] object · 15 fields
id
data:geo:GSE91061
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null
bytes
null
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null
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null
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The datasets analyzed in this study could be found in GSE14520 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14520, in GSE91061 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE91061, and in GSE14502 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14502.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets analyzed in this study could be found in GSE14520 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14520, in GSE91061 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE91061, and in GSE14502 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14502.
access_statement_kind
data_availability_statement
sample_accessions array · 109 items
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sample_count
109
group_sizes
null
group_sizes_basis
null
platform
9052
taxon
Homo sapiens
title
Molecular portraits of tumor mutational and micro-environmental sculpting by immune checkpoint blockade therapy
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 · 6 items
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asset:data:geo:GSE14502 not downloaded
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[3]
asset:data:geo:GSE14520 licence not read
[4]
asset:data:geo:GSE91061 not downloaded
[5]
asset:data:geo:GSE91061 licence not read
analysis object · 4 fields
state
partial
methods array · 2 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
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time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
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quote
KM
[1] object · 10 fields
id
method-2
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null
specific
null
label
Single-sample gene set enrichment analysis (ssGSEA)
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
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verbatim
quote
We employed the ssGSEA approach to determine each patient's IFNγ score to assess the Th1/IFNγ expression variations in metabolic subtypes and enrichment score of 14 oxidative stress-related biological pathways.
targets array · 0 items
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
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assay_families array · 9 items
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gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
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required_operations array · 1 item
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survival_km
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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
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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 · 3 items
[0]
GSE14520
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GSE91061
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GSE14502
resolved_accessions array · 3 items
[0]
GSE14520
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GSE91061
[2]
GSE14502
statements array · 1 item
[0]
The datasets analyzed in this study could be found in GSE14520 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14520, in GSE91061 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE91061, and in GSE14502 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14502.
basis
The paper names GSE14520, GSE91061, GSE14502 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
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survival_km
assets array · 2 items
[0]
source:pmid:36860731
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data:geo:GSE14502
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
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converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE14502
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
2026-11-01T18:32:22Z
independence
single_reader
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method
verbatim
availability
verbatim
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usage object · 3 fields
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[0] object · 4 fields
id
extraction
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entities array · 3 items
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type
paper
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source:pmid:36860731
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manuscript
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PMID 36860731 full text
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id
data:geo:GSE14502
type
dataset
label
GEO GSE14502
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
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type
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PMID 36860731 full text
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type
dataset
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GEO GSE14502
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agent:corpus-assay-engine
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agent:minimax-reader
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accession_resolution
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agent:corpus-assay-engine
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36860731", "kind": "science-record", "revision": 2, "content_hash": "sha256:7a198280855d8f912a11911af831da8de53e2d09485be0625c955316e62433ce", "created_at": "2026-11-01T19:01:29Z", "updated_at": "2026-11-01T21:30:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development of Prognostic Features of Hepatocellular Carcinoma Based on Metabolic Gene Classification and Immune and Oxidative Stress Characteristic Analysis.", "doi": "10.1155/2023/1847700", "pmid": "36860731", "authors": ["Shimeng Cui", "Minghao Zhang", "Shanshan Bai", "Yanfang Bi", "Shan Cong", "Shi Jin", "Shuang Li", "Hui He", "Jian Zhang"], "journal": "Oxidative medicine and cellular longevity", "year": 2023, "abstract": "Background: The molecular classification of HCC premised on metabolic genes might give assistance for diagnosis, therapy, prognosis prediction, immune infiltration, and oxidative stress in addition to supplementing the limitations of the clinical staging system. This would help to better represent the deeper features of HCC.\nMethods: TCGA datasets combined with GSE14520 and HCCDB18 datasets were used to determine the metabolic subtype (MC) using ConsensusClusterPlus. ssGSEA method was used to calculate the IFNγ score, the oxidative stress pathway scores, and the score distribution of 22 distinct immune cells, and their differential expressions were assessed with the use of CIBERSORT. To generate a subtype classification feature index, LDA was utilized. Screening of the metabolic gene coexpression modules was done with the help of WGCNA.\nResults: Three MCs (MC1, MC2, and MC3) were identified and showed different prognoses (MC2-poor and MC1-better). Although MC2 had a high immune microenvironment infiltration, T cell exhaustion markers were expressed at a high level in MC2 in contrast with MC1. Most oxidative stress-related pathways are inhibited in the MC2 subtype and activated in the MC1 subtype. The immunophenotyping of pan-cancer showed that the C1 and C2 subtypes with poor prognosis accounted for significantly higher proportions of MC2 and MC3 subtypes than MC1, while the better prognostic C3 subtype accounted for significantly lower proportions of MC2 than MC1. As per the findings of the TIDE analysis, MC1 had a greater likelihood of benefiting from immunotherapeutic regimens. MC2 was found to have a greater sensitivity to traditional chemotherapy drugs. Finally, 7 potential gene markers indicate HCC prognosis.\nConclusion: The difference (variation) in tumor microenvironment and oxidative stress among metabolic subtypes of HCC was compared from multiple angles and levels. A complete and thorough clarification of the molecular pathological properties of HCC, the exploration of reliable markers for diagnosis, the improvement of the cancer staging system, and the guiding of individualized treatment of HCC all gain benefit greatly from molecular classification associated with metabolism.", "claims": [{"id": "claim-method", "statement": "We employed the ssGSEA approach to determine each patient's IFNγ score to assess the Th1/IFNγ expression variations in metabolic subtypes and enrichment score of 14 oxidative stress-related biological pathways.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36860731", "locator": "sections[6] \"2.4. Single-Sample Gene Set Enrichment Analysis (ssGSEA)\" paragraph 2", "quote": "We employed the ssGSEA approach to determine each patient's IFNγ score to assess the Th1/IFNγ expression variations in metabolic subtypes and enrichment score of 14 oxidative stress-related biological pathways."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed in this study could be found in GSE14520 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14520, in GSE91061 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE91061, and in GSE14502 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14502.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36860731", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "The datasets analyzed in this study could be found in GSE14520 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14520, in GSE91061 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE91061, and in GSE14502 at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14502."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three metabolic HCC subtypes were identified, with MC2 having an unfavorable prognosis and MC1 having a favorable prognosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36860731", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Three MCs (MC1, MC2, and MC3) were identified and showed different prognoses (MC2-poor and MC1-better)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Three metabolic HCC subtypes were identified, with MC2 having an unfavorable prognosis and MC1 having a favorable prognosis.", "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:36860731"], "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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