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pmid:34291084

An Immune-Gene-Based Classifier Predicts Prognosis in Patients With Cervical Squamous Cell Carcinoma.

Huixia Yang · Xiaoyan Han · Zengping Hao

Frontiers in molecular biosciences · 2021 doi:10.3389/fmolb.2021.679474

Paper

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Experiment

complete

Data

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Analysis

partial

Execution

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title
An Immune-Gene-Based Classifier Predicts Prognosis in Patients With Cervical Squamous Cell Carcinoma.
doi
10.3389/fmolb.2021.679474
pmid
34291084
authors array · 3 items
[0]
Huixia Yang
[1]
Xiaoyan Han
[2]
Zengping Hao
journal
Frontiers in molecular biosciences
year
2021
abstract
Objective: Immunity plays a vital role in the human papilloma virus (HPV) persistent infection, and closely associates with occurrence and development of cervical squamous cell carcinoma (CSCC). Herein, we performed an integrated bioinformatics analysis to establish an immune-gene signature and immune-associated nomogram for predicting prognosis of CSCC patients. Methods: The list of immunity-associated genes was retrieved from ImmPort database. The gene and clinical information of CSCC patients were obtained from The Cancer Genome Atlas (TCGA) website. The immune gene signature for predicting overall survival (OS) of CSCC patients was constructed using the univariate Cox-regression analysis, random survival forests, and multivariate Cox-regression analysis. This signature was externally validated in GSE44001 cohort from Gene Expression Omnibus (GEO). Then, based on the established signature and the TCGA cohort with the corresponding clinical information, a nomogram was constructed and evaluated via Cox regression analysis, concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots and decision curve analyses (DCAs). Results: A 5-immune-gene prognostic signature for CSCC was established. Low expression of ICOS, ISG20 and high expression of ANGPTL4, SBDS, LTBR were risk factors for CSCC prognosis indicating poor OS. Based on this signature, the OS was significantly worse in high-risk group than in low-risk group (p-value < 0.001), the area under curves (AUCs) for 1-, 3-, 5-years OS were, respectively, 0.784, 0.727, and 0.715. A nomogram incorporating the risk score of signature and the clinical stage was constructed. The C-index of this nomogram was 0.76. AUC values were 0.811, 0.717, and 0.712 for 1-, 3-, 5-years OS. The nomogram showed good calibration and gained more net benefits than the 5-immune-gene signature and the clinical stage. Conclusion: The 5-immune-gene signature may serve as a novel, independent predictor for prognosis in patients with CSCC. The nomogram incorporating the signature risk score and clinical stage improved the predictive performance than the signature and clinical stage alone for predicting 1-year OS.
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Genetic profiling to predict recurrence of early cervical cancer
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A 5-Immune-gene Prognostic Signature was Established for CSCC Patients
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diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
[1]
roc_curve
[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.8
band
high
quote
ROC analysis
[4] object · 10 fields
id
method-5
family
model_calibration
specific
decision_curve
label
Model calibration / clinical utility
dsl_operations array · 2 items
[0]
calibration_bins
[1]
net_benefit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
predictions_and_outcomes
evidence object · 3 fields
score
0.8
band
high
quote
decision curve analysis
[5] object · 10 fields
id
method-6
family
contingency_analysis
specific
chi_square
label
Categorical (contingency table) analysis
dsl_operations array · 1 item
[0]
chi_square_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
categorical_cross_tabulation
evidence object · 3 fields
score
0.8
band
high
quote
Chi-square
[6] object · 10 fields
id
method-7
family
null
specific
null
label
Univariate Cox-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
reordered
quote
“Firstly, univariate Cox-regression analysis was conducted to identify survival-associated immune genes via R-package “survival” (version 3.2-11).”
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
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 · 1 item
[0]
GSE44001
resolved_accessions array · 1 item
[0]
GSE44001
statements array · 1 item
[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
basis
The paper names GSE44001 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
cox_ph
assets array · 3 items
[0]
source:pmid:34291084
[1]
data:geo:GSE44001
[2]
asset:table:pmid:34291084:1
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:GSE44001
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
2026-10-31T18:32:34Z
independence
single_reader
evidence_check object · 2 fields
method
reordered
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
52246
completion_tokens
1465
cached_tokens
17416
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
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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:34291084
type
paper
label
pmid:34291084
[1] object · 3 fields
id
source:pmid:34291084
type
manuscript
label
PMID 34291084 full text
[2] object · 3 fields
id
data:geo:GSE44001
type
dataset
label
GEO GSE44001
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:34291084
type
paper
label
pmid:34291084
[1] object · 3 fields
id
source:pmid:34291084
type
manuscript
label
PMID 34291084 full text
[2] object · 3 fields
id
data:geo:GSE44001
type
dataset
label
GEO GSE44001
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34291084
type
extraction
used array · 1 item
[0]
source:pmid:34291084
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE44001
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE44001
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:34291084
parent_hash
sha256:8617cd3032f357764174b3e17196a0291e25bbcaf238abdfcb3998bd3122f479
fork_of
null
gaps array · 7 items
[0]
asset:data:geo:GSE44001 licence not read
[1]
asset:data:geo:GSE44001 not downloaded
[2]
execution.not_run
[3]
method.reader_named_unmapped
[4]
review.human_critique
[5]
review.independent_reader
[6]
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
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cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Cox regression
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:34291084", "kind": "science-record", "revision": 7, "content_hash": "sha256:3a164719754b1191ac98f9e3ae17375390052183ef5f42031c4a92d107e90972", "created_at": "2026-11-01T15:41:44Z", "updated_at": "2026-11-01T22:04:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "An Immune-Gene-Based Classifier Predicts Prognosis in Patients With Cervical Squamous Cell Carcinoma.", "doi": "10.3389/fmolb.2021.679474", "pmid": "34291084", "authors": ["Huixia Yang", "Xiaoyan Han", "Zengping Hao"], "journal": "Frontiers in molecular biosciences", "year": 2021, "abstract": "Objective: Immunity plays a vital role in the human papilloma virus (HPV) persistent infection, and closely associates with occurrence and development of cervical squamous cell carcinoma (CSCC). Herein, we performed an integrated bioinformatics analysis to establish an immune-gene signature and immune-associated nomogram for predicting prognosis of CSCC patients. Methods: The list of immunity-associated genes was retrieved from ImmPort database. The gene and clinical information of CSCC patients were obtained from The Cancer Genome Atlas (TCGA) website. The immune gene signature for predicting overall survival (OS) of CSCC patients was constructed using the univariate Cox-regression analysis, random survival forests, and multivariate Cox-regression analysis. This signature was externally validated in GSE44001 cohort from Gene Expression Omnibus (GEO). Then, based on the established signature and the TCGA cohort with the corresponding clinical information, a nomogram was constructed and evaluated via Cox regression analysis, concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots and decision curve analyses (DCAs). Results: A 5-immune-gene prognostic signature for CSCC was established. Low expression of ICOS, ISG20 and high expression of ANGPTL4, SBDS, LTBR were risk factors for CSCC prognosis indicating poor OS. Based on this signature, the OS was significantly worse in high-risk group than in low-risk group (p-value < 0.001), the area under curves (AUCs) for 1-, 3-, 5-years OS were, respectively, 0.784, 0.727, and 0.715. A nomogram incorporating the risk score of signature and the clinical stage was constructed. The C-index of this nomogram was 0.76. AUC values were 0.811, 0.717, and 0.712 for 1-, 3-, 5-years OS. The nomogram showed good calibration and gained more net benefits than the 5-immune-gene signature and the clinical stage. Conclusion: The 5-immune-gene signature may serve as a novel, independent predictor for prognosis in patients with CSCC. The nomogram incorporating the signature risk score and clinical stage improved the predictive performance than the signature and clinical stage alone for predicting 1-year OS.", "claims": [{"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34291084", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "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:34291084"], "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:GSE44001"], "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:GSE44001"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34291084", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2021.679474", "sha256": "sha256:6b865e7ff6f8e79bfa01f2b9e1b77be940ef680bb88e8519e3cae42dae021976", "bytes": 63441, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2021.679474", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8289438", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE44001", "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=GSE44001", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE44001", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. 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