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pmid:38260290

Higher Inflammatory Response in Hepatocellular Carcinoma is Associated with Immune Cell Infiltration and a Better Outcome.

Masanori Oshi · Kohei Chida · Arya Mariam Roy · Gabriella Kim Mann · Nan An · Li Yan · Itaru Endo · Kazuaki Takabe

Research square · 2024 doi:10.21203/rs.3.rs-3768964/v1

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

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pmid:38260290
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2026-11-01T19:20:11Z
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2026-11-01T22:53:31Z
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title
Higher Inflammatory Response in Hepatocellular Carcinoma is Associated with Immune Cell Infiltration and a Better Outcome.
doi
10.21203/rs.3.rs-3768964/v1
pmid
38260290
authors array · 8 items
[0]
Masanori Oshi
[1]
Kohei Chida
[2]
Arya Mariam Roy
[3]
Gabriella Kim Mann
[4]
Nan An
[5]
Li Yan
[6]
Itaru Endo
[7]
Kazuaki Takabe
journal
Research square
year
2024
abstract
Background & Aims: Hepatocellular carcinoma (HCC) often develops from chronic liver inflammation. Inflammation within a tumor can either promote cancer progression or activate an immune response against it. This study aims to determine the clinical significance of enhanced inflammation in HCC. Methods: Data from 655 HCC patients across four cohorts (TCGA, GSE6764, GSE76427, GSE89377) were examined. Inflammatory response was quantified using a scoring system derived from the gene set variation analysis of the "INFLAMMATORY_RESPONSE" gene set. Results: A stepwise increase in inflammatory response was noted from normal liver to cirrhosis, with consistently lower levels in HCC across both GSE6764 and GSE89377 cohorts (both p<0.001). Similar trends were observed in interferon response, pathways such as IL6/JAK/STAT3 and complement signaling, coagulation cascade, and allograft rejection (all p<0.02). HCCs with high inflammatory response were associated with increased immune cell infiltrations (p<0.01) and cytolytic activity (p<0.001). Interestingly, these HCCs had reduced mutation rates, no relationship with cell proliferation, and displayed both immune responses and pro-cancerous signals including epithelial-mesenchymal transition, KRAS, and hypoxia. Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008). Conclusion: HCC with higher levels of inflammatory response demonstrated increased immune cell infiltration, enhanced immune-related and other pro-cancerous-related signaling, and better patient prognosis.
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Survival analysis was performed used log-rank test and Cox proportional hazards.
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sections[7] "Statistical analysis" paragraph 2
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Survival analysis was performed used log-rank test and Cox proportional hazards.
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All the cohorts/datasets used in this study; The Cancer Genome Atlas (TCGA) and GO cohorts are all publicly available without any restrictions via cBioportal or Gene Expression Omnibus (GEO).
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A high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008).
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Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008).
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A high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008).
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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
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 · 3 items
[0]
GSE6764
[1]
GSE76427
[2]
GSE89377
resolved_accessions array · 3 items
[0]
GSE6764
[1]
GSE76427
[2]
GSE89377
statements array · 1 item
[0]
All the cohorts/datasets used in this study; The Cancer Genome Atlas (TCGA) and GO cohorts are all publicly available without any restrictions via cBioportal or Gene Expression Omnibus (GEO).
basis
The paper names GSE6764, GSE76427, GSE89377 in GEO database 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:38260290
[1]
data:geo:GSE6764
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:GSE6764
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
2026-11-01T19:06:15Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
10024
completion_tokens
1569
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:38260290
type
paper
label
pmid:38260290
[1] object · 3 fields
id
source:pmid:38260290
type
manuscript
label
PMID 38260290 full text
[2] object · 3 fields
id
data:geo:GSE6764
type
dataset
label
GEO GSE6764
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:38260290
type
paper
label
pmid:38260290
[1] object · 3 fields
id
source:pmid:38260290
type
manuscript
label
PMID 38260290 full text
[2] object · 3 fields
id
data:geo:GSE6764
type
dataset
label
GEO GSE6764
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-38260290
type
extraction
used array · 1 item
[0]
source:pmid:38260290
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE6764
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE6764
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:38260290
parent_hash
sha256:222c5dc6bf106d346410b324f4f8b0c4f50b798c78499488382d46a17d96b510
fork_of
null
gaps array · 11 items
[0]
asset:data:geo:GSE6764 licence not read
[1]
asset:data:geo:GSE6764 not downloaded
[2]
asset:data:geo:GSE76427 licence not read
[3]
asset:data:geo:GSE76427 not downloaded
[4]
asset:data:geo:GSE89377 licence not read
[5]
asset:data:geo:GSE89377 not downloaded
[6]
execution.not_run
[7]
method.reader_differs_from_extractor
[8]
review.human_critique
[9]
review.independent_reader
[10]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Survival analysis was performed used log-rank test and Cox proportional hazards.
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38260290", "kind": "science-record", "revision": 4, "content_hash": "sha256:e3990b0f444c854b9f267126a0a8182b44a194e86ad06591d04cb033509d62eb", "created_at": "2026-11-01T19:20:11Z", "updated_at": "2026-11-01T22:53:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Higher Inflammatory Response in Hepatocellular Carcinoma is Associated with Immune Cell Infiltration and a Better Outcome.", "doi": "10.21203/rs.3.rs-3768964/v1", "pmid": "38260290", "authors": ["Masanori Oshi", "Kohei Chida", "Arya Mariam Roy", "Gabriella Kim Mann", "Nan An", "Li Yan", "Itaru Endo", "Kazuaki Takabe"], "journal": "Research square", "year": 2024, "abstract": "Background & Aims: Hepatocellular carcinoma (HCC) often develops from chronic liver inflammation. Inflammation within a tumor can either promote cancer progression or activate an immune response against it. This study aims to determine the clinical significance of enhanced inflammation in HCC.\nMethods: Data from 655 HCC patients across four cohorts (TCGA, GSE6764, GSE76427, GSE89377) were examined. Inflammatory response was quantified using a scoring system derived from the gene set variation analysis of the \"INFLAMMATORY_RESPONSE\" gene set.\nResults: A stepwise increase in inflammatory response was noted from normal liver to cirrhosis, with consistently lower levels in HCC across both GSE6764 and GSE89377 cohorts (both p<0.001). Similar trends were observed in interferon response, pathways such as IL6/JAK/STAT3 and complement signaling, coagulation cascade, and allograft rejection (all p<0.02). HCCs with high inflammatory response were associated with increased immune cell infiltrations (p<0.01) and cytolytic activity (p<0.001). Interestingly, these HCCs had reduced mutation rates, no relationship with cell proliferation, and displayed both immune responses and pro-cancerous signals including epithelial-mesenchymal transition, KRAS, and hypoxia. Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008).\nConclusion: HCC with higher levels of inflammatory response demonstrated increased immune cell infiltration, enhanced immune-related and other pro-cancerous-related signaling, and better patient prognosis.", "claims": [{"id": "claim-method", "statement": "Survival analysis was performed used log-rank test and Cox proportional hazards.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38260290", "locator": "sections[7] \"Statistical analysis\" paragraph 2", "quote": "Survival analysis was performed used log-rank test and Cox proportional hazards."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the cohorts/datasets used in this study; The Cancer Genome Atlas (TCGA) and GO cohorts are all publicly available without any restrictions via cBioportal or Gene Expression Omnibus (GEO).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38260290", "locator": "sections[21] \"Data Availability:\" paragraph 2", "quote": "All the cohorts/datasets used in this study; The Cancer Genome Atlas (TCGA) and GO cohorts are all publicly available without any restrictions via cBioportal or Gene Expression Omnibus (GEO)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38260290", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008).", "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:38260290"], "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:GSE6764"], "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:GSE6764"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38260290", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21203/rs.3.rs-3768964/v1", "sha256": "sha256:16f337caeb10d1fa35edae46a66fb37b2f2c33766abc619def1b3d82dd61a3b9", "bytes": 35827, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21203/rs.3.rs-3768964/v1", "version": null, "note": "Full article fetched from PMC; 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