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pmid:34188683

Construction and Validation of a Macrophage-Associated Risk Model for Predicting the Prognosis of Osteosarcoma.

Kang-Wen Xiao · Zhi-Bo Liu · Zi-Hang Zeng · Fei-Fei Yan · Ling-Fei Xiao · Jia-Li Li · Lin Cai

Journal of oncology · 2021 doi:10.1155/2021/9967954

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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:34188683
kind
science-record
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sha256:1b3541dd8f8d7e8dc1d8e2b1f4de6ebc9066faf6db653befc1c39107359c745b
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2026-11-01T15:41:40Z
updated_at
2026-11-01T22:04:04Z
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paper object · 10 fields
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title
Construction and Validation of a Macrophage-Associated Risk Model for Predicting the Prognosis of Osteosarcoma.
doi
10.1155/2021/9967954
pmid
34188683
authors array · 7 items
[0]
Kang-Wen Xiao
[1]
Zhi-Bo Liu
[2]
Zi-Hang Zeng
[3]
Fei-Fei Yan
[4]
Ling-Fei Xiao
[5]
Jia-Li Li
[6]
Lin Cai
journal
Journal of oncology
year
2021
abstract
BACKGROUND: Osteosarcoma is one of the most common bone tumors among children. Tumor-associated macrophages have been found to interact with tumor cells, secreting a variety of cytokines about tumor growth, metastasis, and prognosis. This study aimed to identify macrophage-associated genes (MAGs) signatures to predict the prognosis of osteosarcoma. METHODS: Totally 384 MAGs were collected from GSEA software C7: immunologic signature gene sets. Differential gene expression (DGE) analysis was performed between normal bone samples and osteosarcoma samples in GSE99671. Kaplan-Meier survival analysis was performed to identify prognostic MAGs in TARGET-OS. Decision curve analysis (DCA), nomogram, receiver operating characteristic (ROC), and survival curve analysis were further used to assess our risk model. All genes from TARGET-OS were used for gene set enrichment analysis (GSEA). Immune infiltration of osteosarcoma sample was calculated using CIBERSORT and ESTIMATE packages. The independent test data set GSE21257 from gene expression omnibus (GEO) was used to validate our risk model. RESULTS: 5 MAGs (MAP3K5, PML, WDR1, BAMBI, and GNPDA2) were screened based on protein-protein interaction (PPI), DGE, and survival analysis. A novel macrophage-associated risk model was constructed to predict a risk score based on multivariate Cox regression analysis. The high-risk group showed a worse prognosis of osteosarcoma (p < 0.001) while the low-risk group had higher immune and stromal scores. The risk score was identified as an independent prognostic factor for osteosarcoma. MAGs model for diagnosis of osteosarcoma had a better net clinical benefit based on DCA. The nomogram and ROC curve also effectively predicted the prognosis of osteosarcoma. Besides, the validation result was consistent with the result of TARGET-OS. CONCLUSIONS: A novel macrophage-associated risk score to differentiate low- and high-risk groups of osteosarcoma was constructed based on integrative bioinformatics analysis. Macrophages might affect the prognosis of osteosarcoma through macrophage differentiation pathways and bring novel sights for the progression and prognosis of osteosarcoma.
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The data sets (TARGET-OS, GSE21257, and GSE99671) analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/) and TARGET database (https://ocg.cancer.gov/programs/target).
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sections[24] "Data Availability" paragraph 2
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Genome-wide gene expression profiling on pre-chemotherapy biopsies of osteosarcoma patients who developed metastases within 5yrs (n=34) and patients who did not develop metastases within 5yrs (n=19)
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The data sets (TARGET-OS, GSE21257, and GSE99671) analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/) and TARGET database (https://ocg.cancer.gov/programs/target).
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Whole transcriptome analysis identifies differentially regulated networks between osteosarcoma and normal bone samples
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2.1. Sample Collection and Data Preprocessing
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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
0.7
band
medium
quote
ROC curve
[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
0.7
band
medium
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
targets array · 0 items
gaps array · 0 items
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]
survival_km
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: kaplan_meier.
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]
GSE21257
[1]
GSE99671
resolved_accessions array · 2 items
[0]
GSE21257
[1]
GSE99671
statements array · 1 item
[0]
The data sets (TARGET-OS, GSE21257, and GSE99671) analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/) and TARGET database (https://ocg.cancer.gov/programs/target).
basis
The paper names GSE21257, GSE99671 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]
survival_km
assets array · 6 items
[0]
source:pmid:34188683
[1]
data:geo:GSE21257
[2]
asset:table:pmid:34188683:1
[3]
asset:table:pmid:34188683:2
[4]
asset:table:pmid:34188683:3
[5]
asset:table:pmid:34188683:4
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:GSE21257
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
2026-10-31T19:39:01Z
independence
single_reader
evidence_check object · 2 fields
method
absent
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
42168
completion_tokens
2468
cached_tokens
784
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
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review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
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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:34188683
type
paper
label
pmid:34188683
[1] object · 3 fields
id
source:pmid:34188683
type
manuscript
label
PMID 34188683 full text
[2] object · 3 fields
id
data:geo:GSE21257
type
dataset
label
GEO GSE21257
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:34188683
type
paper
label
pmid:34188683
[1] object · 3 fields
id
source:pmid:34188683
type
manuscript
label
PMID 34188683 full text
[2] object · 3 fields
id
data:geo:GSE21257
type
dataset
label
GEO GSE21257
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34188683
type
extraction
used array · 1 item
[0]
source:pmid:34188683
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE21257
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE21257
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:34188683
parent_hash
sha256:4f25f9027ad8665774dd9b452827397a34c90a4d1678cc8b9b904c5d7d94545e
fork_of
null
gaps array · 8 items
[0]
asset:data:geo:GSE21257 licence not read
[1]
asset:data:geo:GSE21257 not downloaded
[2]
asset:data:geo:GSE99671 licence not read
[3]
asset:data:geo:GSE99671 not downloaded
[4]
execution.not_run
[5]
review.human_critique
[6]
review.independent_reader
[7]
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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survival_km
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
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Kaplan-Meier
order_basis
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id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34188683", "kind": "science-record", "revision": 7, "content_hash": "sha256:1b3541dd8f8d7e8dc1d8e2b1f4de6ebc9066faf6db653befc1c39107359c745b", "created_at": "2026-11-01T15:41:40Z", "updated_at": "2026-11-01T22:04:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction and Validation of a Macrophage-Associated Risk Model for Predicting the Prognosis of Osteosarcoma.", "doi": "10.1155/2021/9967954", "pmid": "34188683", "authors": ["Kang-Wen Xiao", "Zhi-Bo Liu", "Zi-Hang Zeng", "Fei-Fei Yan", "Ling-Fei Xiao", "Jia-Li Li", "Lin Cai"], "journal": "Journal of oncology", "year": 2021, "abstract": "BACKGROUND: Osteosarcoma is one of the most common bone tumors among children. Tumor-associated macrophages have been found to interact with tumor cells, secreting a variety of cytokines about tumor growth, metastasis, and prognosis. This study aimed to identify macrophage-associated genes (MAGs) signatures to predict the prognosis of osteosarcoma.\nMETHODS: Totally 384 MAGs were collected from GSEA software C7: immunologic signature gene sets. Differential gene expression (DGE) analysis was performed between normal bone samples and osteosarcoma samples in GSE99671. Kaplan-Meier survival analysis was performed to identify prognostic MAGs in TARGET-OS. Decision curve analysis (DCA), nomogram, receiver operating characteristic (ROC), and survival curve analysis were further used to assess our risk model. All genes from TARGET-OS were used for gene set enrichment analysis (GSEA). Immune infiltration of osteosarcoma sample was calculated using CIBERSORT and ESTIMATE packages. The independent test data set GSE21257 from gene expression omnibus (GEO) was used to validate our risk model.\nRESULTS: 5 MAGs (MAP3K5, PML, WDR1, BAMBI, and GNPDA2) were screened based on protein-protein interaction (PPI), DGE, and survival analysis. A novel macrophage-associated risk model was constructed to predict a risk score based on multivariate Cox regression analysis. The high-risk group showed a worse prognosis of osteosarcoma (p < 0.001) while the low-risk group had higher immune and stromal scores. The risk score was identified as an independent prognostic factor for osteosarcoma. MAGs model for diagnosis of osteosarcoma had a better net clinical benefit based on DCA. The nomogram and ROC curve also effectively predicted the prognosis of osteosarcoma. Besides, the validation result was consistent with the result of TARGET-OS.\nCONCLUSIONS: A novel macrophage-associated risk score to differentiate low- and high-risk groups of osteosarcoma was constructed based on integrative bioinformatics analysis. Macrophages might affect the prognosis of osteosarcoma through macrophage differentiation pathways and bring novel sights for the progression and prognosis of osteosarcoma.", "claims": [{"id": "claim-data-access", "statement": "The data sets (TARGET-OS, GSE21257, and GSE99671) analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/) and TARGET database (https://ocg.cancer.gov/programs/target).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34188683", "locator": "sections[24] \"Data Availability\" paragraph 2", "quote": "The data sets (TARGET-OS, GSE21257, and GSE99671) analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/) and TARGET database (https://ocg.cancer.gov/programs/target)."}], "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:34188683"], "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:GSE21257"], "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:GSE21257"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34188683", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/9967954", "sha256": 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"identifier": "GSE99671", "version": null, "note": "The data sets (TARGET-OS, GSE21257, and GSE99671) analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/) and TARGET database (https://ocg.cancer.gov/programs/target).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data sets (TARGET-OS, GSE21257, and GSE99671) analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/) and TARGET database (https://ocg.cancer.gov/programs/target).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2649696", "GSM2649697", "GSM2649698", "GSM2649699", "GSM2649700", "GSM2649701", "GSM2649702", "GSM2649703", "GSM2649704", "GSM2649705", "GSM2649706", "GSM2649707", "GSM2649708", "GSM2649709", "GSM2649710", "GSM2649711", "GSM2649712", "GSM2649713", "GSM2649714", "GSM2649715", "GSM2649716", "GSM2649717", "GSM2649718", "GSM2649719", 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