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pmid:36611155

Cuproptosis regulatory genes greatly contribute to clinical assessments of hepatocellular carcinoma.

Changwei Ke · Shejiao Dai · Fangshi Xu · Jia Yuan · Shuting Fan · Yang Chen · Longbao Yang · Yong Li

BMC cancer · 2023 doi:10.1186/s12885-022-10461-2

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Experiment

partial

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pmid:36611155
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title
Cuproptosis regulatory genes greatly contribute to clinical assessments of hepatocellular carcinoma.
doi
10.1186/s12885-022-10461-2
pmid
36611155
authors array · 8 items
[0]
Changwei Ke
[1]
Shejiao Dai
[2]
Fangshi Xu
[3]
Jia Yuan
[4]
Shuting Fan
[5]
Yang Chen
[6]
Longbao Yang
[7]
Yong Li
journal
BMC cancer
year
2023
abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a common abdominal cancer with dissatisfactory therapeutic effects. The discovery of cuproptosis lights on new approach for cancer treatment and assessment. So far, there is extremely limited research investigating the roles of cuproptosis-related (CR) genes in cancers. METHODS: A novel CR risk signature was constructed using the Lasso regression analysis. Its prognostic value was assessed via a series of survival analyses and validated in three GEO cohorts. The effects of CR risk signature on tumor immune microenvironment (TIM) were explored through CIBERSORT, ESTIMATE, and ssGSEA algorithms. Using GESA, we investigated its impacts on various metabolism process. The somatic mutation features of CR signature genes were also explored via cBioPortal database. Using tumor mutation burden, expressions of immune checkpoints, TIDE score, IMvigor 210 cohort, and GSE109211 dataset, we explored the potential associations of CR risk score with the efficacy of immune checkpoint inhibitors (ICIs) and sorafenib. Finally, the biofunctions of DLAT in HCC cells were ascertained through qPCR, immunohistochemistry, colony formation, and Transwell assays. RESULTS: FDX1, DLAT, CDKN2A and GLS constituted the CR risk signature. CR risk signature possessed high prognostic value and was also applicable to three validation cohorts. Meanwhile, it could improve the accuracy and clinical making-decision benefit of traditional prognostic model. Moreover, high CR risk was indicative of unfavorable anti-tumor immune response and active metabolisms of glycolysis and nucleotide. As for therapeutic correlation, CR risk score was a potential biomarker for predicting the efficacy of ICIs and sorafenib. Through qPCR and immunohistochemistry detection in clinical samples, we reconfirmed DLAT was significantly upregulated in HCC samples. Overexpression of DLAT could promote the proliferation, migration, and invasion of HepG2 and HuH-7 cells. CONCLUSIONS: The novel CR risk signature greatly contributed to the clinical assessment of HCC. Cuproptosis regulatory gene DLAT possessed cancer-promoting capacities and was expected to be a promising therapeutic target for HCC.
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Second, we used CR DEGs to accomplish the modeling process through the Lasso regression analysis using the ‘glmnet’ R package.
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Second, we used CR DEGs to accomplish the modeling process through the Lasso regression analysis using the ‘glmnet’ R package.
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The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/). GEO database (https://www.ncbi.nlm.nih.gov/geo/). ICGC database (http://dcc.icgc.org/). GTEx database (https://xenabrowser.net/datapages/). STRING online tool (https://string-db.org/). DAVID online tool (https://david.ncifcrf.gov/). Cutoff Finder online tool (http://molpath.charite.de/cutoff). cBioPortal database (http://cbioportal.org). MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/). TIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).
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sections[36] "Availability of data and materials" paragraphs 1-12
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The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/). GEO database (https://www.ncbi.nlm.nih.gov/geo/). ICGC database (http://dcc.icgc.org/). GTEx database (https://xenabrowser.net/datapages/). STRING online tool (https://string-db.org/). DAVID online tool (https://david.ncifcrf.gov/). Cutoff Finder online tool (http://molpath.charite.de/cutoff). cBioPortal database (http://cbioportal.org). MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/). TIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).
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The Lasso-derived CR risk signature had prognostic value in HCC, with high CR risk conferring a worse prognosis.
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High CR risk conferred a worse prognosis (HR = 2.71, P < 0.001) (Fig. 3A).
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sections[20] "Great prognostic value of CR risk signature" paragraph 2
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High CR risk conferred a worse prognosis (HR = 2.71, P < 0.001) (Fig. 3A).
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The Lasso-derived CR risk signature had prognostic value in HCC, with high CR risk conferring a worse prognosis.
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Molecular predictors of prevention of recurrence in hepatocellular carcinoma with sorafenib as adjuvant treatment in the phase 3 STORM trial
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[487]
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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
gaps array · 6 items
[0]
asset:data:geo:GSE109211 not downloaded
[1]
asset:data:geo:GSE109211 licence not read
[2]
asset:data:geo:GSE116174 not downloaded
[3]
asset:data:geo:GSE116174 licence not read
[4]
asset:data:geo:GSE14520 not downloaded
[5]
asset:data:geo:GSE14520 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
id
method-1
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group_comparison
specific
wilcoxon
label
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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
band
high
quote
Wilcoxon
[1] object · 10 fields
id
method-2
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principal_component_analysis
specific
pca
label
Principal component analysis
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[0]
pca_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
wide_numeric_matrix
evidence object · 3 fields
score
0.8
band
high
quote
PCA
[2] object · 10 fields
id
method-3
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null
specific
null
label
Lasso regression analysis
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
Second, we used CR DEGs to accomplish the modeling process through the Lasso regression analysis using the ‘glmnet’ R package.
targets array · 2 items
[0] object · 8 fields
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target-published-estimate
claim_id
claim-target-result
operation
group_comparison_wilcoxon
unit
hazard ratio
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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
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target-published-estimate-p-value
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claim-target-result
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group_comparison_wilcoxon
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 · 2 items
[0]
method.reader_named_unmapped
[1]
method.group_comparison_wilcoxon
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
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[0]
meta_analysis
[1]
machine_learning
[2]
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[3]
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[4]
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[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
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
false
required_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon.
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]
GSE14520
[1]
GSE116174
[2]
GSE109211
resolved_accessions array · 3 items
[0]
GSE14520
[1]
GSE116174
[2]
GSE109211
statements array · 1 item
[0]
The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows: TCGA database (https://portal.gdc.cancer.gov/). GEO database (https://www.ncbi.nlm.nih.gov/geo/). ICGC database (http://dcc.icgc.org/). GTEx database (https://xenabrowser.net/datapages/). STRING online tool (https://string-db.org/). DAVID online tool (https://david.ncifcrf.gov/). Cutoff Finder online tool (http://molpath.charite.de/cutoff). cBioPortal database (http://cbioportal.org). MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/). TIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).
basis
The paper names GSE14520, GSE116174, GSE109211 in 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 · 0 items
assets array · 2 items
[0]
source:pmid:36611155
[1]
data:geo:GSE109211
steps array · 0 items
must_build object · 5 fields
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[0] object · 3 fields
operation
group_comparison_wilcoxon
priority
null
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readers array · 0 items
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[0]
data:geo:GSE109211
gaps array · 0 items
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
provider_family
minimax
read_at
2026-11-01T18:22:37Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
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5
usage object · 3 fields
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20193
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2231
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128
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[0] object · 4 fields
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extraction
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complete
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MiniMax-M3.1-Flash
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[1]
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[2]
review.human_critique
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not_run
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null
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[0]
execution.not_run
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[0] object · 3 fields
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pmid:36611155
type
paper
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pmid:36611155
[1] object · 3 fields
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source:pmid:36611155
type
manuscript
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PMID 36611155 full text
[2] object · 3 fields
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data:geo:GSE109211
type
dataset
label
GEO GSE109211
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
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pmid:36611155
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paper
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pmid:36611155
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source:pmid:36611155
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manuscript
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PMID 36611155 full text
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data:geo:GSE109211
type
dataset
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GEO GSE109211
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agent:corpus-assay-engine
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activity-read-36611155
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[0]
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agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE109211
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agent:corpus-assay-engine
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343fb30756ba6ec3
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parent_id
pmid:36611155
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sha256:ac9768d444e49f0cfdba7e708c800a8460023b4283de01d07db618e41f8b60b8
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[1]
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[2]
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[3]
asset:data:geo:GSE116174 not downloaded
[4]
asset:data:geo:GSE14520 licence not read
[5]
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[6]
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[7]
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[12]
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[0] object · 11 fields
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99e1195c7d6f
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partial
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99e1195c7d6f
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0.99
evidence array · 4 items
[0]
f DLAT in HCC cells were ascertained through qPCR, immunohistochemistry, colony formation, and
[1]
the efficacy of ICIs and sorafenib. Through qPCR and immunohistochemistry detection in clinic
[2]
PrimeScript RT reagent Kit (Takara, Japan). RT-qPCR reaction was marked by SYBR-Green PCR Reagen
[3]
Materials and methods Clinical samples and qPCR After obtaining informed consent from the pa
order_basis
paper_text_order:1189
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in HCC cells were ascertained through qPCR, immunohistochemistry, colony formation, and Transwell assays. RES
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cacy of ICIs and sorafenib. Through qPCR and immunohistochemistry detection in clinical samples, we reconfirme
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paper_text_order:1196
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he proliferation, migration, and invasion of HepG2 and HuH-7 cells. CONCLUSIONS: The novel CR r
[1]
itro experiments. HepG2 and Huh-7 cells were cultured in MEM (Minimum Essential Medium) and DMEM (Dul
[2]
ection Two hepatocellular cancer cell lines (HepG2 and Huh-7) that were obtained from Procell L
[3]
were used for further in vitro experiments. HepG2 and Huh-7 cells were cultured in MEM (Minimu
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paper_text_order:2016
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n in Supplementary table 4. Cell culture and transfection Two hepatocellular cancer cell lines (HepG2
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able 5. The lentiviral system created stable transfected cells (HanHeng Biotechnology, Shanghai, Chin
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paper_text_order:3199
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36611155", "kind": "science-record", "revision": 3, "content_hash": "sha256:4216779637ab76ce4bcef9e5dd2edb6d290e0205d116dc81fee98e7237356aa5", "created_at": "2026-11-01T19:01:09Z", "updated_at": "2026-11-01T22:08:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cuproptosis regulatory genes greatly contribute to clinical assessments of hepatocellular carcinoma.", "doi": "10.1186/s12885-022-10461-2", "pmid": "36611155", "authors": ["Changwei Ke", "Shejiao Dai", "Fangshi Xu", "Jia Yuan", "Shuting Fan", "Yang Chen", "Longbao Yang", "Yong Li"], "journal": "BMC cancer", "year": 2023, "abstract": "BACKGROUND: Hepatocellular carcinoma (HCC) is a common abdominal cancer with dissatisfactory therapeutic effects. The discovery of cuproptosis lights on new approach for cancer treatment and assessment. So far, there is extremely limited research investigating the roles of cuproptosis-related (CR) genes in cancers.\nMETHODS: A novel CR risk signature was constructed using the Lasso regression analysis. Its prognostic value was assessed via a series of survival analyses and validated in three GEO cohorts. The effects of CR risk signature on tumor immune microenvironment (TIM) were explored through CIBERSORT, ESTIMATE, and ssGSEA algorithms. Using GESA, we investigated its impacts on various metabolism process. The somatic mutation features of CR signature genes were also explored via cBioPortal database. Using tumor mutation burden, expressions of immune checkpoints, TIDE score, IMvigor 210 cohort, and GSE109211 dataset, we explored the potential associations of CR risk score with the efficacy of immune checkpoint inhibitors (ICIs) and sorafenib. Finally, the biofunctions of DLAT in HCC cells were ascertained through qPCR, immunohistochemistry, colony formation, and Transwell assays.\nRESULTS: FDX1, DLAT, CDKN2A and GLS constituted the CR risk signature. CR risk signature possessed high prognostic value and was also applicable to three validation cohorts. Meanwhile, it could improve the accuracy and clinical making-decision benefit of traditional prognostic model. Moreover, high CR risk was indicative of unfavorable anti-tumor immune response and active metabolisms of glycolysis and nucleotide. As for therapeutic correlation, CR risk score was a potential biomarker for predicting the efficacy of ICIs and sorafenib. Through qPCR and immunohistochemistry detection in clinical samples, we reconfirmed DLAT was significantly upregulated in HCC samples. Overexpression of DLAT could promote the proliferation, migration, and invasion of HepG2 and HuH-7 cells.\nCONCLUSIONS: The novel CR risk signature greatly contributed to the clinical assessment of HCC. Cuproptosis regulatory gene DLAT possessed cancer-promoting capacities and was expected to be a promising therapeutic target for HCC.", "claims": [{"id": "claim-method", "statement": "Second, we used CR DEGs to accomplish the modeling process through the Lasso regression analysis using the ‘glmnet’ R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36611155", "locator": "sections[6] \"Establishment of CR risk signature\" paragraph 2", "quote": "Second, we used CR DEGs to accomplish the modeling process through the Lasso regression analysis using the ‘glmnet’ R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows:\nTCGA database (https://portal.gdc.cancer.gov/).\nGEO database (https://www.ncbi.nlm.nih.gov/geo/).\nICGC database (http://dcc.icgc.org/).\nGTEx database (https://xenabrowser.net/datapages/).\nSTRING online tool (https://string-db.org/).\nDAVID online tool (https://david.ncifcrf.gov/).\nCutoff Finder online tool (http://molpath.charite.de/cutoff).\ncBioPortal database (http://cbioportal.org).\nMSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/).\nTIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36611155", "locator": "sections[36] \"Availability of data and materials\" paragraphs 1-12", "quote": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows:\nTCGA database (https://portal.gdc.cancer.gov/).\nGEO database (https://www.ncbi.nlm.nih.gov/geo/).\nICGC database (http://dcc.icgc.org/).\nGTEx database (https://xenabrowser.net/datapages/).\nSTRING online tool (https://string-db.org/).\nDAVID online tool (https://david.ncifcrf.gov/).\nCutoff Finder online tool (http://molpath.charite.de/cutoff).\ncBioPortal database (http://cbioportal.org).\nMSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/).\nTIDE scoring system online tool (http://tide.dfci.harvard.edu/login/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The Lasso-derived CR risk signature had prognostic value in HCC, with high CR risk conferring a worse prognosis.", "kind": "quantitative", "target": {"value": 2.71, "unit": "hazard ratio", "tolerance": null, "source": "High CR risk conferred a worse prognosis (HR = 2.71, P < 0.001) (Fig. 3A)."}, "evidence": [{"asset": "source:pmid:36611155", "locator": "sections[20] \"Great prognostic value of CR risk signature\" paragraph 2", "quote": "High CR risk conferred a worse prognosis (HR = 2.71, P < 0.001) (Fig. 3A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The Lasso-derived CR risk signature had prognostic value in HCC, with high CR risk conferring a worse 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:36611155"], "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:GSE109211"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE109211"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36611155", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-022-10461-2", "sha256": "sha256:aa71d92b71b8c9c8dff13ed93e7a1e0777cb051c32bb06cb424e298d5471258e", "bytes": 72421, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-022-10461-2", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9824945", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE109211", "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=GSE109211", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE109211", "version": null, "note": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows:\nTCGA database (https://portal.gdc.cancer.gov/).\nGEO database (https://www.ncbi.nlm.nih.gov/geo/).\nICGC database (http://dcc.icgc.org/).\nGTEx database (https://xenabrowser.net/datapages/).\nSTRING online tool (https://string-db.org/).\nDAVID online tool (https://david.ncifcrf.gov/).\nCutoff Finder online tool (http://molpath.charite.de/cutoff).\ncBioPortal database (http://cbioportal.org).\nMSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/).\nTIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows:\nTCGA database (https://portal.gdc.cancer.gov/).\nGEO database (https://www.ncbi.nlm.nih.gov/geo/).\nICGC database (http://dcc.icgc.org/).\nGTEx database (https://xenabrowser.net/datapages/).\nSTRING online tool (https://string-db.org/).\nDAVID online tool (https://david.ncifcrf.gov/).\nCutoff Finder online tool (http://molpath.charite.de/cutoff).\ncBioPortal database (http://cbioportal.org).\nMSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/).\nTIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2935278", "GSM2935279", "GSM2935280", "GSM2935281", "GSM2935282", "GSM2935283", "GSM2935284", "GSM2935285", "GSM2935286", "GSM2935287", "GSM2935288", "GSM2935289", "GSM2935290", "GSM2935291", "GSM2935292", "GSM2935293", "GSM2935294", "GSM2935295", "GSM2935296", "GSM2935297", "GSM2935298", "GSM2935299", "GSM2935300", "GSM2935301", "GSM2935302", "GSM2935303", "GSM2935304", "GSM2935305", "GSM2935306", "GSM2935307", "GSM2935308", "GSM2935309", "GSM2935310", "GSM2935311", "GSM2935312", "GSM2935313", "GSM2935314", "GSM2935315", "GSM2935316", "GSM2935317", "GSM2935318", "GSM2935319", "GSM2935320", "GSM2935321", "GSM2935322", "GSM2935323", "GSM2935324", "GSM2935325", "GSM2935326", "GSM2935327", "GSM2935328", "GSM2935329", "GSM2935330", "GSM2935331", "GSM2935332", "GSM2935333", "GSM2935334", "GSM2935335", "GSM2935336", "GSM2935337", "GSM2935338", "GSM2935339", "GSM2935340", "GSM2935341", "GSM2935342", "GSM2935343", "GSM2935344", "GSM2935345", "GSM2935346", "GSM2935347", "GSM2935348", "GSM2935349", "GSM2935350", "GSM2935351", "GSM2935352", "GSM2935353", "GSM2935354", "GSM2935355", "GSM2935356", "GSM2935357", "GSM2935358", "GSM2935359", "GSM2935360", "GSM2935361", "GSM2935362", "GSM2935363", "GSM2935364", "GSM2935365", "GSM2935366", "GSM2935367", "GSM2935368", "GSM2935369", "GSM2935370", "GSM2935371", "GSM2935372", "GSM2935373", "GSM2935374", "GSM2935375", "GSM2935376", "GSM2935377", "GSM2935378", "GSM2935379", "GSM2935380", "GSM2935381", "GSM2935382", "GSM2935383", "GSM2935384", "GSM2935385", "GSM2935386", "GSM2935387", "GSM2935388", "GSM2935389", "GSM2935390", "GSM2935391", "GSM2935392", "GSM2935393", "GSM2935394", "GSM2935395", "GSM2935396", "GSM2935397", "GSM2935398", "GSM2935399", "GSM2935400", "GSM2935401", "GSM2935402", "GSM2935403", "GSM2935404", "GSM2935405", "GSM2935406", "GSM2935407", "GSM2935408", "GSM2935409", "GSM2935410", "GSM2935411", "GSM2935412", "GSM2935413", "GSM2935414", "GSM2935415", "GSM2935416", "GSM2935417"], "sample_count": 140, "group_sizes": null, "group_sizes_basis": null, "platform": "13938", "taxon": "Homo sapiens", "title": "Molecular predictors of prevention of recurrence in hepatocellular carcinoma with sorafenib as adjuvant treatment in the phase 3 STORM trial", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE116174", "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=GSE116174", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE116174", "version": null, "note": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows:\nTCGA database (https://portal.gdc.cancer.gov/).\nGEO database (https://www.ncbi.nlm.nih.gov/geo/).\nICGC database (http://dcc.icgc.org/).\nGTEx database (https://xenabrowser.net/datapages/).\nSTRING online tool (https://string-db.org/).\nDAVID online tool (https://david.ncifcrf.gov/).\nCutoff Finder online tool (http://molpath.charite.de/cutoff).\ncBioPortal database (http://cbioportal.org).\nMSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/).\nTIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows:\nTCGA database (https://portal.gdc.cancer.gov/).\nGEO database (https://www.ncbi.nlm.nih.gov/geo/).\nICGC database (http://dcc.icgc.org/).\nGTEx database (https://xenabrowser.net/datapages/).\nSTRING online tool (https://string-db.org/).\nDAVID online tool (https://david.ncifcrf.gov/).\nCutoff Finder online tool (http://molpath.charite.de/cutoff).\ncBioPortal database (http://cbioportal.org).\nMSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/).\nTIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3212448", "GSM3212449", "GSM3212450", "GSM3212451", "GSM3212452", "GSM3212453", "GSM3212454", "GSM3212455", "GSM3212456", "GSM3212457", "GSM3212458", "GSM3212459", "GSM3212460", "GSM3212461", "GSM3212462", "GSM3212463", "GSM3212464", "GSM3212465", "GSM3212466", "GSM3212467", "GSM3212468", "GSM3212469", "GSM3212470", "GSM3212471", "GSM3212472", "GSM3212473", "GSM3212474", "GSM3212475", "GSM3212476", "GSM3212477", "GSM3212478", "GSM3212479", "GSM3212480", "GSM3212481", "GSM3212482", "GSM3212483", "GSM3212484", "GSM3212485", "GSM3212486", "GSM3212487", "GSM3212488", "GSM3212489", "GSM3212490", "GSM3212491", "GSM3212492", "GSM3212493", "GSM3212494", "GSM3212495", "GSM3212496", "GSM3212497", "GSM3212498", "GSM3212499", "GSM3212500", "GSM3212501", "GSM3212502", "GSM3212503", "GSM3212504", "GSM3212505", "GSM3212506", "GSM3212507", "GSM3212508", "GSM3212509", "GSM3212510", "GSM3212511"], "sample_count": 64, "group_sizes": null, "group_sizes_basis": null, "platform": "13158", "taxon": "Homo sapiens", "title": "Gene expression profile in human 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}}, {"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 datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows:\nTCGA database (https://portal.gdc.cancer.gov/).\nGEO database (https://www.ncbi.nlm.nih.gov/geo/).\nICGC database (http://dcc.icgc.org/).\nGTEx database (https://xenabrowser.net/datapages/).\nSTRING online tool (https://string-db.org/).\nDAVID online tool (https://david.ncifcrf.gov/).\nCutoff Finder online tool (http://molpath.charite.de/cutoff).\ncBioPortal database (http://cbioportal.org).\nMSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/).\nTIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows:\nTCGA database (https://portal.gdc.cancer.gov/).\nGEO database (https://www.ncbi.nlm.nih.gov/geo/).\nICGC database (http://dcc.icgc.org/).\nGTEx database (https://xenabrowser.net/datapages/).\nSTRING online tool (https://string-db.org/).\nDAVID online tool (https://david.ncifcrf.gov/).\nCutoff Finder online tool (http://molpath.charite.de/cutoff).\ncBioPortal database (http://cbioportal.org).\nMSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/).\nTIDE scoring system online tool (http://tide.dfci.harvard.edu/login/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM362947", "GSM362948", "GSM362949", "GSM362950", "GSM362951", "GSM362952", "GSM362953", "GSM362954", "GSM362955", "GSM362956", "GSM362957", "GSM362958", "GSM362959", "GSM362960", "GSM362961", "GSM362962", "GSM362963", "GSM362964", "GSM362965", "GSM362966", "GSM362967", "GSM362968", "GSM362969", "GSM362970", "GSM362971", 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"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}}], "gaps": ["asset:data:geo:GSE109211 not downloaded", "asset:data:geo:GSE109211 licence not read", "asset:data:geo:GSE116174 not downloaded", "asset:data:geo:GSE116174 licence not read", "asset:data:geo:GSE14520 not downloaded", "asset:data:geo:GSE14520 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": 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No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "group_comparison_wilcoxon", "expected_value": 0.001, "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": ["method.reader_named_unmapped", "method.group_comparison_wilcoxon"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "capability": {"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": {"tier": "R1", "reachable": true, "accessions": ["GSE14520", "GSE116174", "GSE109211"], "resolved_accessions": ["GSE14520", "GSE116174", "GSE109211"], "statements": ["The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. All databases in the present study are open, as follows:\nTCGA database (https://portal.gdc.cancer.gov/).\nGEO database (https://www.ncbi.nlm.nih.gov/geo/).\nICGC database (http://dcc.icgc.org/).\nGTEx database (https://xenabrowser.net/datapages/).\nSTRING online tool (https://string-db.org/).\nDAVID online tool (https://david.ncifcrf.gov/).\nCutoff Finder online tool (http://molpath.charite.de/cutoff).\ncBioPortal database (http://cbioportal.org).\nMSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/).\nTIDE scoring system online tool (http://tide.dfci.harvard.edu/login/)."], "basis": "The paper names GSE14520, GSE116174, GSE109211 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:36611155", "data:geo:GSE109211"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE109211"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:22:37Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 20193, "completion_tokens": 2231, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36611155", "type": "paper", "label": "pmid:36611155"}, {"id": "source:pmid:36611155", "type": "manuscript", "label": "PMID 36611155 full text"}, {"id": "data:geo:GSE109211", "type": "dataset", "label": "GEO GSE109211"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36611155", "type": "paper", "label": "pmid:36611155"}, {"id": "source:pmid:36611155", "type": "manuscript", "label": "PMID 36611155 full text"}, {"id": "data:geo:GSE109211", "type": "dataset", "label": "GEO GSE109211"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36611155", "type": "extraction", "used": ["source:pmid:36611155"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE109211", "type": "accession_resolution", "used": ["data:geo:GSE109211"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"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": {"parent_id": "pmid:36611155", "parent_hash": "sha256:ac9768d444e49f0cfdba7e708c800a8460023b4283de01d07db618e41f8b60b8", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE109211 licence not read", "asset:data:geo:GSE109211 not downloaded", "asset:data:geo:GSE116174 licence not read", "asset:data:geo:GSE116174 not downloaded", "asset:data:geo:GSE14520 licence not read", "asset:data:geo:GSE14520 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["f DLAT in HCC cells were ascertained through qPCR, immunohistochemistry, colony formation, and", "the efficacy of ICIs and sorafenib. Through qPCR and immunohistochemistry detection in clinic", "PrimeScript RT reagent Kit (Takara, Japan). RT-qPCR reaction was marked by SYBR-Green PCR Reagen", "Materials and methods Clinical samples and qPCR After obtaining informed consent from the pa"], "order_basis": "paper_text_order:1189", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["in HCC cells were ascertained through qPCR, immunohistochemistry, colony formation, and Transwell assays. RES", "cacy of ICIs and sorafenib. Through qPCR and immunohistochemistry detection in clinical samples, we reconfirme"], "order_basis": "paper_text_order:1196", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["he proliferation, migration, and invasion of HepG2 and HuH-7 cells. CONCLUSIONS: The novel CR r", "itro experiments. HepG2 and Huh-7 cells were cultured in MEM (Minimum Essential Medium) and DMEM (Dul", "ection Two hepatocellular cancer cell lines (HepG2 and Huh-7) that were obtained from Procell L", "were used for further in vitro experiments. HepG2 and Huh-7 cells were cultured in MEM (Minimu"], "order_basis": "paper_text_order:2016", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["n in Supplementary table 4. Cell culture and transfection Two hepatocellular cancer cell lines (HepG2", "able 5. The lentiviral system created stable transfected cells (HanHeng Biotechnology, Shanghai, Chin"], "order_basis": "paper_text_order:3199", "id": "assay:4"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}