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pmid:35966307

Development of novel gene signatures for the risk stratification of prognosis and diagnostic prediction of osteosarcoma patients using bioinformatics analysis.

Guoquan Li · Baoliang Huang · Hao Wu · Hu Zhang

Translational cancer research · 2022 doi:10.21037/tcr-22-1706

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complete

Experiment

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Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:35966307
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2026-11-01T18:15:04Z
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2026-11-01T22:49:47Z
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title
Development of novel gene signatures for the risk stratification of prognosis and diagnostic prediction of osteosarcoma patients using bioinformatics analysis.
doi
10.21037/tcr-22-1706
pmid
35966307
authors array · 4 items
[0]
Guoquan Li
[1]
Baoliang Huang
[2]
Hao Wu
[3]
Hu Zhang
journal
Translational cancer research
year
2022
abstract
Background: Osteosarcoma (OS) is a common malignant bone cancer in children and teenagers that originates from osteoblast cells. Although many biomarkers have been reported in OS, they have not improved the prognosis of this disease. This study sought to identify effective biomarkers for the early diagnosis and prognosis of OS using a comprehensive bioinformatics analysis. Methods: OS-associated microRNAs (miRNAs) were screened in the Human microRNA Disease Database (HMDD). The differentially expressed genes (DEGs) related to OS were screened using 3 data sets (GSE16088, GSE36001, and GSE56001) from the Gene Expression Omnibus (GEO) database. By comparing the targets of these miRNAs with DEGs in response to OS, we identified OS-associated candidate genes. The gene expression and clinical data of 96 OS samples with complete clinical information was downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Comprehensive bioinformatics analyses, including univariate, multivariate Cox, and Kaplan-Meier (KM) analyses were conducted based on these data to identify the prognostic genes and construct prognostic signature for OS survival and recurrence. Logistic regression analysis was performed based on the GSE42352 data set (including 103 OS and 15 normal samples) to develop a diagnostic model for OS. Results: By comparing the DEGs and predicted targets of the 28 OS survival-associated miRNAs, we identified 267 OS-associated candidate genes. Additionally, 14 genes were found to be significantly associated with the survival of OS patients. Finally, 3 genes [i.e., signal transducer and activators of transcription factor 4 (STAT4), heat shock protein family E member 1 (HSPE1), and actin-related protein 2/3 complex subunit 5 (ARPC5)] were integrated into a prognostic index. The 3-gene signature was an independent factor for OS survival [hazard ratio (HR) =1.699; P<0.001] and recurrence (HR =2.532; P=0.004) and was found to have an excellent predictive performance [area under the receiver operating characteristic (ROC) curve (AUC) >0.7]. Additionally, 2 genes (i.e., STAT4 and HSPE1) were identified to be associated with OS diagnosis (P<0.05). This 2-gene diagnostic signature for OS presented a good discriminative power (AUC =0.981) and the error between the predicted and actual value was 0.029. Conclusions: We constructed a 3-gene prognostic signature and a 2-gene diagnostic signature that have the potential to assist in prognosis predicting and diagnosis of OS in clinic.
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Univariate and multivariate Cox analyses were performed to examine the prognostic value of the prognostic gene signature.
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sections[9] "Statistical analysis" paragraph 2
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Univariate and multivariate Cox analyses were performed to examine the prognostic value of the prognostic gene signature.
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In this study, 180 miRNAs related to OS and 67 miRNAs associated with the prognosis of OS were downloaded from the HMDD.
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sections[4] "Selection of potential prognosis-related genes in OS" paragraph 2
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In this study, 180 miRNAs related to OS and 67 miRNAs associated with the prognosis of OS were downloaded from the HMDD.
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We constructed a 3-gene prognostic signature and a 2-gene diagnostic signature that have the potential to assist in prognosis predicting and diagnosis of OS in clinic.
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Gene expression profiles of human osteosarcoma
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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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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
1
band
verbatim
quote
Univariate and multivariate Cox analyses were performed to examine the prognostic value of the prognostic gene signature.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[0]
logrank_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
log-rank
[2] object · 10 fields
id
method-3
family
regression_modelling
specific
logistic
label
Regression modelling
dsl_operations array · 1 item
[0]
glm_logit_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
predictors_and_outcome
evidence object · 3 fields
score
0.7
band
medium
quote
Logistic regression
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 · 6 items
[0]
GSE16088
[1]
GSE36001
[2]
GSE56001
[3]
GSE21257
[4]
GSE42352
[5]
GSE19276
resolved_accessions array · 6 items
[0]
GSE16088
[1]
GSE36001
[2]
GSE56001
[3]
GSE21257
[4]
GSE42352
[5]
GSE19276
statements array · 1 item
[0]
In this study, 180 miRNAs related to OS and 67 miRNAs associated with the prognosis of OS were downloaded from the HMDD.
basis
The paper names GSE16088, GSE36001, GSE56001, GSE21257, GSE42352, GSE19276 in 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]
survival_km
assets array · 2 items
[0]
source:pmid:35966307
[1]
data:geo:GSE16088
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:GSE16088
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T17:59:52Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
null
calls
5
usage object · 3 fields
prompt_tokens
9816
completion_tokens
1755
cached_tokens
264
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:35966307
type
paper
label
pmid:35966307
[1] object · 3 fields
id
source:pmid:35966307
type
manuscript
label
PMID 35966307 full text
[2] object · 3 fields
id
data:geo:GSE16088
type
dataset
label
GEO GSE16088
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:35966307
type
paper
label
pmid:35966307
[1] object · 3 fields
id
source:pmid:35966307
type
manuscript
label
PMID 35966307 full text
[2] object · 3 fields
id
data:geo:GSE16088
type
dataset
label
GEO GSE16088
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-35966307
type
extraction
used array · 1 item
[0]
source:pmid:35966307
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE16088
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE16088
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:35966307
parent_hash
sha256:561a1b5d501dc6c59179630be8d71a606f9db19d46adef57d6520a4670b8ee00
fork_of
null
gaps array · 16 items
[0]
asset:data:geo:GSE16088 licence not read
[1]
asset:data:geo:GSE16088 not downloaded
[2]
asset:data:geo:GSE19276 licence not read
[3]
asset:data:geo:GSE19276 not downloaded
[4]
asset:data:geo:GSE21257 licence not read
[5]
asset:data:geo:GSE21257 not downloaded
[6]
asset:data:geo:GSE36001 licence not read
[7]
asset:data:geo:GSE36001 not downloaded
[8]
asset:data:geo:GSE42352 licence not read
[9]
asset:data:geo:GSE42352 not downloaded
[10]
asset:data:geo:GSE56001 licence not read
[11]
asset:data:geo:GSE56001 not downloaded
[12]
execution.not_run
[13]
review.human_critique
[14]
review.independent_reader
[15]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
survival_km
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Univariate and multivariate Cox analyses were performed to examine the prognostic value of the prognostic gene signature.
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:35966307", "kind": "science-record", "revision": 4, "content_hash": "sha256:c08a502fe69fd9bad3807b6133bd677ecc5a158a278a52443bc282a371d6150e", "created_at": "2026-11-01T18:15:04Z", "updated_at": "2026-11-01T22:49:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development of novel gene signatures for the risk stratification of prognosis and diagnostic prediction of osteosarcoma patients using bioinformatics analysis.", "doi": "10.21037/tcr-22-1706", "pmid": "35966307", "authors": ["Guoquan Li", "Baoliang Huang", "Hao Wu", "Hu Zhang"], "journal": "Translational cancer research", "year": 2022, "abstract": "Background: Osteosarcoma (OS) is a common malignant bone cancer in children and teenagers that originates from osteoblast cells. Although many biomarkers have been reported in OS, they have not improved the prognosis of this disease. This study sought to identify effective biomarkers for the early diagnosis and prognosis of OS using a comprehensive bioinformatics analysis.\nMethods: OS-associated microRNAs (miRNAs) were screened in the Human microRNA Disease Database (HMDD). The differentially expressed genes (DEGs) related to OS were screened using 3 data sets (GSE16088, GSE36001, and GSE56001) from the Gene Expression Omnibus (GEO) database. By comparing the targets of these miRNAs with DEGs in response to OS, we identified OS-associated candidate genes. The gene expression and clinical data of 96 OS samples with complete clinical information was downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Comprehensive bioinformatics analyses, including univariate, multivariate Cox, and Kaplan-Meier (KM) analyses were conducted based on these data to identify the prognostic genes and construct prognostic signature for OS survival and recurrence. Logistic regression analysis was performed based on the GSE42352 data set (including 103 OS and 15 normal samples) to develop a diagnostic model for OS.\nResults: By comparing the DEGs and predicted targets of the 28 OS survival-associated miRNAs, we identified 267 OS-associated candidate genes. Additionally, 14 genes were found to be significantly associated with the survival of OS patients. Finally, 3 genes [i.e., signal transducer and activators of transcription factor 4 (STAT4), heat shock protein family E member 1 (HSPE1), and actin-related protein 2/3 complex subunit 5 (ARPC5)] were integrated into a prognostic index. The 3-gene signature was an independent factor for OS survival [hazard ratio (HR) =1.699; P<0.001] and recurrence (HR =2.532; P=0.004) and was found to have an excellent predictive performance [area under the receiver operating characteristic (ROC) curve (AUC) >0.7]. Additionally, 2 genes (i.e., STAT4 and HSPE1) were identified to be associated with OS diagnosis (P<0.05). This 2-gene diagnostic signature for OS presented a good discriminative power (AUC =0.981) and the error between the predicted and actual value was 0.029.\nConclusions: We constructed a 3-gene prognostic signature and a 2-gene diagnostic signature that have the potential to assist in prognosis predicting and diagnosis of OS in clinic.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate Cox analyses were performed to examine the prognostic value of the prognostic gene signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35966307", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "Univariate and multivariate Cox analyses were performed to examine the prognostic value of the prognostic gene signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "In this study, 180 miRNAs related to OS and 67 miRNAs associated with the prognosis of OS were downloaded from the HMDD.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35966307", "locator": "sections[4] \"Selection of potential prognosis-related genes in OS\" paragraph 2", "quote": "In this study, 180 miRNAs related to OS and 67 miRNAs associated with the prognosis of OS were downloaded from the HMDD."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study constructed a 3-gene prognostic signature for osteosarcoma survival and recurrence and a 2-gene diagnostic signature for osteosarcoma diagnosis using public-database data.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35966307", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We constructed a 3-gene prognostic signature and a 2-gene diagnostic signature that have the potential to assist in prognosis predicting and diagnosis of OS in clinic."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study constructed a 3-gene prognostic signature for osteosarcoma survival and recurrence and a 2-gene diagnostic signature for osteosarcoma diagnosis using public-database data.", "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:35966307"], "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:GSE16088"], "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:GSE16088"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35966307", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tcr-22-1706", "sha256": 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HMDD.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "In this study, 180 miRNAs related to OS and 67 miRNAs associated with the prognosis of OS were downloaded from the HMDD.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM402684", "GSM402685", "GSM402686", "GSM402687", "GSM402688", "GSM402689", "GSM402690", "GSM402691", "GSM402692", "GSM402693", "GSM402694", "GSM402695", "GSM402696", "GSM402697", "GSM402698", "GSM402699", "GSM402700", "GSM402701", "GSM402702", "GSM402703", "GSM402704", "GSM402705", "GSM402706"], "sample_count": 23, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Gene expression profiles of human osteosarcoma", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE19276", "role": "raw", 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"GSM531312", "GSM531313", "GSM531314", "GSM531319", "GSM531320", "GSM531321", "GSM531322", "GSM531323", "GSM531324", "GSM531325", "GSM531326", "GSM531327", "GSM531328", "GSM531329", "GSM531330", "GSM531331", "GSM531332", "GSM531333", "GSM531334", "GSM531335", "GSM531351", "GSM531352"], "sample_count": 53, "group_sizes": null, "group_sizes_basis": null, "platform": "10295", "taxon": "Homo sapiens", "title": "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)", "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:GSE36001", "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=GSE36001", "sha256": null, "bytes": 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