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pmid:33005178

Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma.

Denggang Fu · Biyu Zhang · Lei Yang · Shaoxin Huang · Wang Xin

Frontiers in genetics · 2020 doi:10.3389/fgene.2020.00978

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Experiment

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Data

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33005178
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science-record
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2026-11-01T15:41:12Z
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2026-11-01T22:45:25Z
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paper object · 10 fields
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complete
title
Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma.
doi
10.3389/fgene.2020.00978
pmid
33005178
authors array · 5 items
[0]
Denggang Fu
[1]
Biyu Zhang
[2]
Lei Yang
[3]
Shaoxin Huang
[4]
Wang Xin
journal
Frontiers in genetics
year
2020
abstract
Lung squamous cell carcinoma (LSCC) is the most common subtype of non-small cell lung cancer. Immunotherapy has become an effective treatment in recent years, while patients showed different responses to the current treatment. It is vital to identify the potential immunogenomic signatures to predict patient' prognosis. The expression profiles of LSCC patients with the clinical information were downloaded from TCGA database. Differentially expressed immune-related genes (IRGs) were extracted using edgeR algorithm, and functional enrichment analysis showed that these IRGs were primarily enriched in inflammatory- and immune-related processes. "Cytokine-cytokine receptor interaction" and "PI3K-AKT signaling pathway" were the most enriched KEGG pathways. 27 differentially expressed IRGs were significantly correlated with the overall survival (OS) of patients using univariate Cox regression analysis. A prognostic risk signature that comprises seven IRGs (GCCR, FGF8, CLEC4M, PTH, SLC10A2, NPPC, and FGF4) was developed with effective predictive performance by multivariable Cox stepwise regression analysis. Most importantly, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters, and also validated in two independent LSCC cohorts (GSE4573 and GSE17710). Potential molecular mechanisms and tumor immune landscape of these IRGs were investigated through computational biology. Analysis of tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinct immune landscape in high- and low-risk group. The study was the first time to construct IRG-based immune signature in the recognition of disease progression and prognosis of LSCC patients.
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The differentially expressed genes were identified between the LSCC and adjacent non-tumor samples by edgeR R package (Robinson et al., 2010).
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sections[4] "Identification of the Differentially Expressed Genes (DEGs) and IRGs" paragraph 2
quote
The differentially expressed genes were identified between the LSCC and adjacent non-tumor samples by edgeR R package (Robinson et al., 2010).
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Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. Clinical information of these patients was also downloaded and extracted.
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sections[3] "Gene Expression Datasets and IRGs" paragraph 2
quote
Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. Clinical information of these patients was also downloaded and extracted.
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Human lung squamous cell carcinoma expression profiling
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Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. Clinical information of these patients was also downloaded and extracted.
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Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. Clinical information of these patients was also downloaded and extracted.
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Gene expression signatures for predicting prognosis of squamous cell lung carcinomas
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OS-related differentially expressed IRGs in LSCC patients by univariate Cox regression hazard analysis (P < 0.05).
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PMC7485220
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13
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Correlation of Individual Differentially Expressed IRGs With OS
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TABLE 1
caption
OS-related differentially expressed IRGs in LSCC patients by univariate Cox regression hazard analysis (P < 0.05).
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[0]
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[3]
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[2]
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–2.75875
[3]
0.005802
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2.699299
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2.61468
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2.583223
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1.177088
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2.497194
[3]
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2.486447
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[2]
2.472845
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[2]
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[3]
0.014054
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2.173913
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0.029712
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2.022781
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2.019389
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0.043447
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2.018298
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0.04356
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1.986496
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0.046978
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1.984636
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0.047185
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Key regulated factor of OS-related IRGs in LSCC patients.
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Construction of Transcription Factors (TFs) Regulatory Network
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TABLE 2
caption
Key regulated factor of OS-related IRGs in LSCC patients.
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v-rel reticuloendotheliosis viral oncogene homolog A (avian)
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0.000218
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Univariate and multivariate Cox regression analysis of the risk score and clinical parameters in LSCC patients.
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PMC7485220
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15
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Development and Validation of the Immune Related Prognostic Signature
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TABLE 3
caption
Univariate and multivariate Cox regression analysis of the risk score and clinical parameters in LSCC patients.
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[1]
HR (95% CI)
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HR (95% CI)
[4]
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[2]
0.0116
[3]
1.0158 (1.0007–1.0311)
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0.0405
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pM
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1.2810 (1.0533–1.5580)
[2]
0.0131
[3]
1.2609 (1.0328–1.5395)
[4]
0.0228
[4] array · 5 items
[0]
pN
[1]
1.1680 (0.9839–1.3866)
[2]
0.0761
[3]
1.0929 (0.8826–1.3533)
[4]
0.415
[5] array · 5 items
[0]
pT
[1]
1.3538 (1.1272–1.6259)
[2]
0.0012
[3]
1.3019 (1.0287–1.6476)
[4]
0.0281
[6] array · 5 items
[0]
Gender
[1]
0.8031 (0.5752–1.1213)
[2]
0.1978
[3]
0.8395 (0.5981–1.1783)
[4]
0.3118
[7] array · 5 items
[0]
Tobacco_smoking_history
[1]
0.8829 (0.7805–0.9987)
[2]
0.0476
[3]
0.8667 (0.7634–0.9841)
[4]
0.0273
[8] array · 5 items
[0]
Tumor_stage
[1]
1.2859 (1.1008–1.5020)
[2]
0.0015
[3]
1.0861 (0.8593–1.3729)
[4]
0.4895
[9] array · 5 items
[0]
Tigarettes_exposures (per_day)
[1]
1.0021 (0.9295–1.0803)
[2]
0.9571
[3]
1.0079 (0.9345–1.0870)
[4]
0.8388
[10] array · 5 items
[0]
Risk score
[1]
1.5196 (1.3462–1.7155)
[2]
1.32E–11
[3]
1.5480 (1.3577–1.7649)
[4]
6.62E-11
locator
section[15]/table-wrap[1]#T3
gaps array · 4 items
[0]
asset:data:geo:GSE17710 not downloaded
[1]
asset:data:geo:GSE17710 licence not read
[2]
asset:data:geo:GSE4573 not downloaded
[3]
asset:data:geo:GSE4573 licence not read
analysis object · 4 fields
state
partial
methods array · 3 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
edger
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
The differentially expressed genes were identified between the LSCC and adjacent non-tumor samples by edgeR R package (Robinson et al., 2010).
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
Kaplan-Meier
[2] object · 10 fields
id
method-3
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
band
medium
quote
Cox regression
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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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: edger.
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]
GSE4573
[1]
GSE17710
resolved_accessions array · 2 items
[0]
GSE4573
[1]
GSE17710
statements array · 1 item
[0]
Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. Clinical information of these patients was also downloaded and extracted.
basis
The paper names GSE4573, GSE17710 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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 5 items
[0]
source:pmid:33005178
[1]
data:geo:GSE17710
[2]
asset:table:pmid:33005178:1
[3]
asset:table:pmid:33005178:2
[4]
asset:table:pmid:33005178:3
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:GSE17710
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
2026-10-31T19:12:10Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
null
calls
3
usage object · 3 fields
prompt_tokens
50666
completion_tokens
1720
cached_tokens
776
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:33005178
type
paper
label
pmid:33005178
[1] object · 3 fields
id
source:pmid:33005178
type
manuscript
label
PMID 33005178 full text
[2] object · 3 fields
id
data:geo:GSE17710
type
dataset
label
GEO GSE17710
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:33005178
type
paper
label
pmid:33005178
[1] object · 3 fields
id
source:pmid:33005178
type
manuscript
label
PMID 33005178 full text
[2] object · 3 fields
id
data:geo:GSE17710
type
dataset
label
GEO GSE17710
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-33005178
type
extraction
used array · 1 item
[0]
source:pmid:33005178
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE17710
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE17710
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:33005178
parent_hash
sha256:ee6b4c670237154a6d3795c97f6f012c236cf8a3761f766cd721441f85abc957
fork_of
null
gaps array · 9 items
[0]
asset:data:geo:GSE17710 licence not read
[1]
asset:data:geo:GSE17710 not downloaded
[2]
asset:data:geo:GSE4573 licence not read
[3]
asset:data:geo:GSE4573 not downloaded
[4]
execution.not_run
[5]
method.reader_differs_from_extractor
[6]
review.human_critique
[7]
review.independent_reader
[8]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
differential_expression
definition_version
f2132e96ae6c7a4e
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The differentially expressed genes were identified between the LSCC and adjacent non-tumor samples by edgeR R package (Robinson et al., 2010).
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:33005178", "kind": "science-record", "revision": 9, "content_hash": "sha256:2da735c424894ab51a0632fc81e6feb09128a1c4643bd45ddb857d0aadd208cf", "created_at": "2026-11-01T15:41:12Z", "updated_at": "2026-11-01T22:45:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma.", "doi": "10.3389/fgene.2020.00978", "pmid": "33005178", "authors": ["Denggang Fu", "Biyu Zhang", "Lei Yang", "Shaoxin Huang", "Wang Xin"], "journal": "Frontiers in genetics", "year": 2020, "abstract": "Lung squamous cell carcinoma (LSCC) is the most common subtype of non-small cell lung cancer. Immunotherapy has become an effective treatment in recent years, while patients showed different responses to the current treatment. It is vital to identify the potential immunogenomic signatures to predict patient' prognosis. The expression profiles of LSCC patients with the clinical information were downloaded from TCGA database. Differentially expressed immune-related genes (IRGs) were extracted using edgeR algorithm, and functional enrichment analysis showed that these IRGs were primarily enriched in inflammatory- and immune-related processes. \"Cytokine-cytokine receptor interaction\" and \"PI3K-AKT signaling pathway\" were the most enriched KEGG pathways. 27 differentially expressed IRGs were significantly correlated with the overall survival (OS) of patients using univariate Cox regression analysis. A prognostic risk signature that comprises seven IRGs (GCCR, FGF8, CLEC4M, PTH, SLC10A2, NPPC, and FGF4) was developed with effective predictive performance by multivariable Cox stepwise regression analysis. Most importantly, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters, and also validated in two independent LSCC cohorts (GSE4573 and GSE17710). Potential molecular mechanisms and tumor immune landscape of these IRGs were investigated through computational biology. Analysis of tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinct immune landscape in high- and low-risk group. The study was the first time to construct IRG-based immune signature in the recognition of disease progression and prognosis of LSCC patients.", "claims": [{"id": "claim-method", "statement": "The differentially expressed genes were identified between the LSCC and adjacent non-tumor samples by edgeR R package (Robinson et al., 2010).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33005178", "locator": "sections[4] \"Identification of the Differentially Expressed Genes (DEGs) and IRGs\" paragraph 2", "quote": "The differentially expressed genes were identified between the LSCC and adjacent non-tumor samples by edgeR R package (Robinson et al., 2010)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. Clinical information of these patients was also downloaded and extracted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33005178", "locator": "sections[3] \"Gene Expression Datasets and IRGs\" paragraph 2", "quote": "Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. Clinical information of these patients was also downloaded and extracted."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33005178"], "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:GSE17710"], "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:GSE17710"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33005178", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2020.00978", "sha256": "sha256:9460d83bbd95cc5a60ca718d8dee67efedc04fe4f17c7556defd18238217c3eb", "bytes": 66092, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2020.00978", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7485220", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17710", "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=GSE17710", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17710", "version": null, "note": "Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. Clinical information of these patients was also downloaded and extracted.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. Clinical information of these patients was also downloaded and extracted.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM442070", "GSM442071", "GSM442072", "GSM442073", "GSM442074", "GSM442075", "GSM442076", "GSM442077", "GSM442078", "GSM442079", "GSM442080", "GSM442081", "GSM442082", "GSM442083", "GSM442084", "GSM442085", "GSM442086", "GSM442087", "GSM442088", "GSM442089", "GSM442090", "GSM442091", "GSM442092", "GSM442093", "GSM442094", "GSM442095", "GSM442096", "GSM442097", "GSM442098", "GSM442099", "GSM442100", "GSM442101", "GSM442102", "GSM442103", "GSM442104", "GSM442105", "GSM442106", "GSM442107", "GSM442108", "GSM442109", "GSM442110", "GSM442111", "GSM442112", "GSM442113", "GSM442114", "GSM442115", "GSM442116", "GSM442117", "GSM442118", "GSM442119", "GSM442120", "GSM442121", "GSM442122", "GSM442123", "GSM442124", "GSM442125"], "sample_count": 56, "group_sizes": null, "group_sizes_basis": null, "platform": "9053", "taxon": "Homo sapiens", "title": "Human lung squamous cell carcinoma expression profiling", "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:GSE4573", "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=GSE4573", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE4573", "version": null, "note": "Level 3 RNA-seq raw count data from 502 lung squamous cell carcinoma patients (LSCC) and 49 non-tumor samples were downloaded from the TCGA database. 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