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pmid:34988018

Identification and Validation of Hub Genes Associated with Bladder Cancer by Integrated Bioinformatics and Experimental Assays.

Kang Chen · Ji Xing · Weimin Yu · Yuqi Xia · Yunlong Zhang · Fan Cheng · Ting Rao

Frontiers in oncology · 2021 doi:10.3389/fonc.2021.782981

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Experiment

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Data

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pmid:34988018
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title
Identification and Validation of Hub Genes Associated with Bladder Cancer by Integrated Bioinformatics and Experimental Assays.
doi
10.3389/fonc.2021.782981
pmid
34988018
authors array · 7 items
[0]
Kang Chen
[1]
Ji Xing
[2]
Weimin Yu
[3]
Yuqi Xia
[4]
Yunlong Zhang
[5]
Fan Cheng
[6]
Ting Rao
journal
Frontiers in oncology
year
2021
abstract
Bladder cancer (BC) is the most common malignant tumor of the urinary system and is associated with high morbidity and mortality; however, the molecular mechanism underlying its occurrence is not clear. In this study, the gene expression profile and related clinical information of GSE13507 were downloaded from the Gene Expression Omnibus (GEO) database. RNA sequencing (RNA-seq) expression data and related clinical information were retrieved from The Cancer Genome Atlas (TCGA) database. Overlapping genes were identified by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). Then, we carried out functional enrichment analysis to understand the potential biological functions of these co-expressed genes. Finally, we performed a protein-protein interaction (PPI) analysis combined with survival analysis. Using the CytoHubba plug-in of Cytoscape, TROAP, CENPF, PRC1, AURKB, CCNB2, CDC20, TTK, CEP55, ASPM, and CDCA8 were identified as candidate central genes. According to the survival analysis, the high expression of TTK was related to the poor overall survival (OS) of patients with BC. TTK may also affect the bladder tumor microenvironment (TME) by affecting the number of immune cells. The expression level of TTK was verified by immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR), and the tumor-promoting effect of TTK in BC cells was confirmed in vitro. Our results also identified the MSC-AS1/hsa-miR-664b-3p/TTK regulatory axis, which may also play an important role in the progression of BC, but further research is needed to verify this result. In summary, our results provide a new idea for accurate early diagnosis, clinical treatment, and prognosis of BC.
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To verify the prognostic value of hub genes, we used the survival package in R software to conduct Kaplan–Meier univariate survival analysis based on the data in TCGA to explore the relationship between overall survival (OS) and hub gene expression.
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sections[8] "Verification of the Prognostic Value of Hub Genes" paragraph 2
quote
To verify the prognostic value of hub genes, we used the survival package in R software to conduct Kaplan–Meier univariate survival analysis based on the data in TCGA to explore the relationship between overall survival (OS) and hub gene expression.
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sections[31] "Data Availability Statement" paragraph 2
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The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.
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High TTK expression was significantly associated with poor overall survival in bladder cancer patients (p < 0.05).
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The analysis showed that, among the 10 hub genes, only the expression level of TTK was significantly correlated with OS in BC patients (p < 0.05; Figures 6A–J ).
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sections[25] "Verification of the Prognostic Value of 10 Hub Genes" paragraph 2
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The analysis showed that, among the 10 hub genes, only the expression level of TTK was significantly correlated with OS in BC patients (p < 0.05; Figures 6A–J ).
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sections[25] "Verification of the Prognostic Value of 10 Hub Genes" paragraph 2
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Our results showed that the high expression of TTK indicates worse prognosis of patients with BC.
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High TTK expression was significantly associated with poor overall survival in bladder cancer patients (p < 0.05).
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title
Predective Value of Prognosis-Related Gene Expression Study in Primary Bladder Cancer
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[307]
GSM814359
sample_count
308
group_sizes
null
group_sizes_basis
null
platform
6947
taxon
Homo sapiens
title
A Molecular Taxonomy of Urothelial Carcinoma
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 · 4 items
[0]
asset:data:geo:GSE13507 not downloaded
[1]
asset:data:geo:GSE13507 licence not read
[2]
asset:data:geo:GSE32894 not downloaded
[3]
asset:data:geo:GSE32894 licence not read
analysis object · 4 fields
state
partial
methods array · 3 items
[0] object · 10 fields
id
method-1
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network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
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[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
protein-protein interaction
[1] object · 10 fields
id
method-2
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network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
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[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
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[0]
edge_list
evidence object · 3 fields
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0.8
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high
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GO enrichment
[2] object · 10 fields
id
method-3
family
null
specific
null
label
Kaplan–Meier univariate survival analysis
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missing_operations array · 0 items
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evidence object · 3 fields
score
1
band
verbatim
quote
To verify the prognostic value of hub genes, we used the survival package in R software to conduct Kaplan–Meier univariate survival analysis based on the data in TCGA to explore the relationship between overall survival (OS) and hub gene expression.
targets array · 1 item
[0] object · 8 fields
id
target-published-estimate
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claim-target-result
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build_graph
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 · 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
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readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
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R1
expressible
true
required_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
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: ppi_network.
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]
GSE13507
[1]
GSE32894
resolved_accessions array · 2 items
[0]
GSE13507
[1]
GSE32894
statements array · 1 item
[0]
The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.
basis
The paper names GSE13507, GSE32894 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 · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
assets array · 2 items
[0]
source:pmid:34988018
[1]
data:geo:GSE13507
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
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capabilities array · 0 items
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[0]
data:geo:GSE13507
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
2026-11-01T17:14:29Z
independence
single_reader
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method
verbatim
availability
verbatim
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5
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11304
completion_tokens
1504
cached_tokens
256
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[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
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minimax
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[0]
review.independent_reader
[1]
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[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:34988018
type
paper
label
pmid:34988018
[1] object · 3 fields
id
source:pmid:34988018
type
manuscript
label
PMID 34988018 full text
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id
data:geo:GSE13507
type
dataset
label
GEO GSE13507
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:34988018
type
paper
label
pmid:34988018
[1] object · 3 fields
id
source:pmid:34988018
type
manuscript
label
PMID 34988018 full text
[2] object · 3 fields
id
data:geo:GSE13507
type
dataset
label
GEO GSE13507
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34988018
type
extraction
used array · 1 item
[0]
source:pmid:34988018
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE13507
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE13507
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agent:corpus-assay-engine
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[0] object · 3 fields
id
agent:corpus-assay-engine
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software
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Corpus assay engine
[1] object · 3 fields
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agent:minimax-reader
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software
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MiniMax literature reader
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reading-sci-2026-11-01
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343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
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ba34b49490d9bfaf
lineage object · 4 fields
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pmid:34988018
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sha256:19148affec9fe6db88ba27c459d7dc3e394d4a4c6cb70aff137c3835ef1d34e3
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null
gaps array · 9 items
[0]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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assays array · 5 items
[0] object · 11 fields
role
data_generation
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rna_seq
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99e1195c7d6f
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partial
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99e1195c7d6f
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0.99
evidence array · 2 items
[0]
sion Omnibus (GEO) database. RNA sequencing (RNA-seq) expression data and related clinical inform
[1]
the Gene Expression Omnibus (GEO) database. RNA sequencing (RNA-seq) expression data and related clinic
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paper_text_order:440
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assay:1
[1] object · 11 fields
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data_generation
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partial
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99e1195c7d6f
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0.99
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[0]
The expression level of TTK was verified by immunohistochemistry (IHC) and real-time quantitative polymerase
[1]
of TTK was verified by immunohistochemistry (IHC) and real-time quantitative polymerase chain
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paper_text_order:1369
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assay:2
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99e1195c7d6f
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0.99
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[0]
time quantitative polymerase chain reaction (RT-qPCR), and the tumor-promoting effect of TTK in B
[1]
e quantitative polymerase chain reaction (RT-qPCR), and the tumor-promoting effect of TTK in B
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paper_text_order:1449
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assay:3
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data_generation
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cell_culture
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99e1195c7d6f
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99e1195c7d6f
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[0]
nghai, Chinese Academy of Sciences, and were cultured in Roswell Park Memorial Institute (RPMI) 1640
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paper_text_order:2062
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assay:4
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analysis
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network_analysis
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34988018", "kind": "science-record", "revision": 4, "content_hash": "sha256:f6de4a13ccd43baa25918d9dcdc9231c1d4eba28c83644550433f5f749910e83", "created_at": "2026-11-01T17:36:42Z", "updated_at": "2026-11-01T22:05:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of Hub Genes Associated with Bladder Cancer by Integrated Bioinformatics and Experimental Assays.", "doi": "10.3389/fonc.2021.782981", "pmid": "34988018", "authors": ["Kang Chen", "Ji Xing", "Weimin Yu", "Yuqi Xia", "Yunlong Zhang", "Fan Cheng", "Ting Rao"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "Bladder cancer (BC) is the most common malignant tumor of the urinary system and is associated with high morbidity and mortality; however, the molecular mechanism underlying its occurrence is not clear. In this study, the gene expression profile and related clinical information of GSE13507 were downloaded from the Gene Expression Omnibus (GEO) database. RNA sequencing (RNA-seq) expression data and related clinical information were retrieved from The Cancer Genome Atlas (TCGA) database. Overlapping genes were identified by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). Then, we carried out functional enrichment analysis to understand the potential biological functions of these co-expressed genes. Finally, we performed a protein-protein interaction (PPI) analysis combined with survival analysis. Using the CytoHubba plug-in of Cytoscape, TROAP, CENPF, PRC1, AURKB, CCNB2, CDC20, TTK, CEP55, ASPM, and CDCA8 were identified as candidate central genes. According to the survival analysis, the high expression of TTK was related to the poor overall survival (OS) of patients with BC. TTK may also affect the bladder tumor microenvironment (TME) by affecting the number of immune cells. The expression level of TTK was verified by immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR), and the tumor-promoting effect of TTK in BC cells was confirmed in vitro. Our results also identified the MSC-AS1/hsa-miR-664b-3p/TTK regulatory axis, which may also play an important role in the progression of BC, but further research is needed to verify this result. In summary, our results provide a new idea for accurate early diagnosis, clinical treatment, and prognosis of BC.", "claims": [{"id": "claim-method", "statement": "To verify the prognostic value of hub genes, we used the survival package in R software to conduct Kaplan–Meier univariate survival analysis based on the data in TCGA to explore the relationship between overall survival (OS) and hub gene expression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34988018", "locator": "sections[8] \"Verification of the Prognostic Value of Hub Genes\" paragraph 2", "quote": "To verify the prognostic value of hub genes, we used the survival package in R software to conduct Kaplan–Meier univariate survival analysis based on the data in TCGA to explore the relationship between overall survival (OS) and hub gene expression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34988018", "locator": "sections[31] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . 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