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pmid:33285689

Identification of candidate biomarkers correlated with the pathogenesis and prognosis of breast cancer via integrated bioinformatics analysis.

Shuyu Liu · Xinkui Liu · Jiarui Wu · Wei Zhou · Mengwei Ni · Ziqi Meng · Shanshan Jia · Jingyuan Zhang · Siyu Guo · Shan Lu · Yingfei Li

Medicine · 2020 doi:10.1097/MD.0000000000023153

Paper

complete

Experiment

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Data

partial

Analysis

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title
Identification of candidate biomarkers correlated with the pathogenesis and prognosis of breast cancer via integrated bioinformatics analysis.
doi
10.1097/MD.0000000000023153
pmid
33285689
authors array · 11 items
[0]
Shuyu Liu
[1]
Xinkui Liu
[2]
Jiarui Wu
[3]
Wei Zhou
[4]
Mengwei Ni
[5]
Ziqi Meng
[6]
Shanshan Jia
[7]
Jingyuan Zhang
[8]
Siyu Guo
[9]
Shan Lu
[10]
Yingfei Li
journal
Medicine
year
2020
abstract
BACKGROUND: This study was carried out to identify potential key genes associated with the pathogenesis and prognosis of breast cancer (BC). METHODS: Seven GEO datasets (GSE24124, GSE32641, GSE36295, GSE42568, GSE53752, GSE70947, GSE109169) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between BC and normal breast tissue samples were screened by an integrated analysis of multiple gene expression profile datasets. Hub genes related to the pathogenesis and prognosis of BC were verified by employing protein-protein interaction (PPI) network. RESULTS: Ten hub genes with high degree were identified, including CDK1, CDC20, CCNA2, CCNB1, CCNB2, BUB1, BUB1B, CDCA8, KIF11, and TOP2A. Lastly, the Kaplan-Meier plotter (KM plotter) online database demonstrated that higher expression levels of these genes were related to lower overall survival. Experimental validation showed that all 10 hub genes had the same expression trend as predicted. CONCLUSION: The findings of this research would provide some directive significance for further investigating the diagnostic and prognostic biomarkers to facilitate the molecular targeting therapy of BC, which could be used as a new biomarker for diagnosis and to guide the combination medicine of BC.
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Limma package in R language was used to analyze the DEGs in BC samples compared with normal samples.[6] Gene integration for the DEGs identified from the 7 datasets was conducted employing RobustRankAggreg.[7]
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Limma package in R language was used to analyze the DEGs in BC samples compared with normal samples.[6] Gene integration for the DEGs identified from the 7 datasets was conducted employing RobustRankAggreg.[7]
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The datasets generated during and/or analyzed during the current study are publicly available.
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null
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The datasets generated during and/or analyzed during the current study are publicly available.
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The datasets generated during and/or analyzed during the current study are publicly available.
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76
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7264
taxon
Homo sapiens
title
Molecular characteristics and metastasis predictor genes of triple-negative breast cancer (II)
resolution_checked_at
2026-11-01T15:39:54Z
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data:geo:GSE70947
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The datasets generated during and/or analyzed during the current study are publicly available.
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[20]
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[23]
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[24]
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[25]
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[26]
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[28]
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[29]
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[30]
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[31]
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[32]
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[50]
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[55]
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[60]
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[70]
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[71]
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[72]
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[73]
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[74]
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[75]
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[76]
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[77]
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[78]
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[79]
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[80]
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[81]
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[82]
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[83]
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[84]
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[85]
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[86]
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[87]
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[88]
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[89]
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[90]
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[91]
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[92]
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[100]
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[104]
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[105]
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[106]
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[107]
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[110]
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[112]
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[113]
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[114]
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[119]
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[120]
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[121]
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[122]
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[123]
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[124]
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[152]
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[154]
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[155]
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[156]
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[160]
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[161]
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[162]
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[163]
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[164]
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[165]
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[166]
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[167]
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[170]
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[171]
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[172]
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[206]
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[212]
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[214]
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[215]
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[216]
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[295]
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sample_count
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null
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13607
taxon
Homo sapiens
title
Age and estrogen-dependent inflammation in breast adenocarcinoma and normal breast tissue [cohort_2]
resolution_checked_at
2026-11-01T15:39:55Z
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identifier_resolution_only_no_download_no_licence_read
downloaded
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[7] object · 16 fields
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Hub genes with high degree of connectivity.
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PPI and module analysis
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Table 2
caption
Hub genes with high degree of connectivity.
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[0]
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section[12]/table-wrap[1]#T2
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structure object · 5 fields
pmcid
PMC7717725
section_index
10
section_title
Identification of DEGs
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column_count
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table object · 8 fields
label
Table 1
caption
Information for the 7 GEO datasets included in the current study.
rows array · 8 items
[0] array · 4 items
[0]
Dataset
[1]
Reference
[2]
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[3]
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[1] array · 4 items
[0]
GSE24124
[1]
Liu et al, 2014
[2]
GPL887-Agilent-012097 Human 1A Microarray (V2) G4110B (Feature Number version)
[3]
119 (99/20)
[2] array · 4 items
[0]
GSE32641
[1]
Liu et al, 2014
[2]
GPL887-Agilent-012097 Human 1A Microarray (V2) G4110B (Feature Number version)
[3]
102 (95/7)
[3] array · 4 items
[0]
GSE36295
[1]
Manikandan J et al, 2018
[2]
GPL6244-[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]
[3]
50 (45/5)
[4] array · 4 items
[0]
GSE42568
[1]
Clarke C et al, 2019
[2]
GPL570-[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
[3]
121 (104/17)
[5] array · 4 items
[0]
GSE53752
[1]
Kuo et al, 2014
[2]
GPL7264-Agilent-012097 Human 1A Microarray (V2) G4110B (Probe Name version)
[3]
76 (51/25)
[6] array · 4 items
[0]
GSE70947
[1]
Quigley et al, 2018
[2]
GPL13607-Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version)
[3]
296 (148/148)
[7] array · 4 items
[0]
GSE109169
[1]
Chang et al, 2019
[2]
GPL5175-[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]
[3]
50 (25/25)
locator
section[10]/table-wrap[1]#T1
[9] object · 16 fields
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asset:table:pmid:33285689:3
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jats-table
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read_table
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note
Hub genes with high degree of connectivity.
structure object · 5 fields
pmcid
PMC7717725
section_index
12
section_title
PPI and module analysis
row_count
11
column_count
4
table object · 8 fields
label
Table 2
caption
Hub genes with high degree of connectivity.
rows array · 11 items
[0] array · 4 items
[0]
Gene
[1]
Degree
[2]
Type
[3]
MCODE cluster
[1] array · 4 items
[0]
CDK1
[1]
75
[2]
up
[3]
Module 1
[2] array · 4 items
[0]
CDC20
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63
[2]
up
[3]
Module 1
[3] array · 4 items
[0]
CCNA2
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[3]
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[0]
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[3]
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[0]
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up
[3]
Module 1
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[0]
BUB1
[1]
58
[2]
up
[3]
Module 1
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[0]
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up
[3]
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[0]
CDCA8
[1]
52
[2]
up
[3]
Module 1
[9] array · 4 items
[0]
TOP2A
[1]
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up
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[0]
KIF11
[1]
50
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section[12]/table-wrap[1]#T2
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[11]
asset:data:geo:GSE70947 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
id
method-1
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differential_expression
specific
limma_voom
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Differential expression analysis
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[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
Limma package in R language was used to analyze the DEGs in BC samples compared with normal samples.[6] Gene integration for the DEGs identified from the 7 datasets was conducted employing RobustRankAggreg.[7]
[1] object · 10 fields
id
method-2
family
survival_analysis
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kaplan_meier
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Survival analysis
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[0]
survival_km
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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
Kaplan-Meier
[2] object · 10 fields
id
method-3
family
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
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
protein-protein interaction
[3] object · 10 fields
id
method-4
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.8
band
high
quote
pathway enrichment
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: limma_voom.
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 · 7 items
[0]
GSE24124
[1]
GSE32641
[2]
GSE36295
[3]
GSE42568
[4]
GSE53752
[5]
GSE70947
[6]
and GSE109169
resolved_accessions array · 6 items
[0]
GSE24124
[1]
GSE32641
[2]
GSE36295
[3]
GSE42568
[4]
GSE53752
[5]
GSE70947
statements array · 1 item
[0]
The datasets generated during and/or analyzed during the current study are publicly available.
basis
The paper names GSE24124, GSE32641, GSE36295, GSE42568, GSE53752, GSE70947 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]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 5 items
[0]
source:pmid:33285689
[1]
data:geo:GSE24124
[2]
asset:table:pmid:33285689:1
[3]
asset:table:pmid:33285689:2
[4]
asset:table:pmid:33285689:3
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:GSE24124
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
2026-10-31T18:25:01Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
23501
completion_tokens
1568
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
[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:33285689
type
paper
label
pmid:33285689
[1] object · 3 fields
id
source:pmid:33285689
type
manuscript
label
PMID 33285689 full text
[2] object · 3 fields
id
data:geo:GSE24124
type
dataset
label
GEO GSE24124
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:33285689
type
paper
label
pmid:33285689
[1] object · 3 fields
id
source:pmid:33285689
type
manuscript
label
PMID 33285689 full text
[2] object · 3 fields
id
data:geo:GSE24124
type
dataset
label
GEO GSE24124
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-33285689
type
extraction
used array · 1 item
[0]
source:pmid:33285689
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE24124
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE24124
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:33285689
parent_hash
sha256:3b7aac41f138339044efdd16e62eecc6e6711ad333cfaa9fd6890d026cb0d3be
fork_of
null
gaps array · 17 items
[0]
asset:data:geo:GSE24124 licence not read
[1]
asset:data:geo:GSE24124 not downloaded
[2]
asset:data:geo:GSE32641 licence not read
[3]
asset:data:geo:GSE32641 not downloaded
[4]
asset:data:geo:GSE36295 licence not read
[5]
asset:data:geo:GSE36295 not downloaded
[6]
asset:data:geo:GSE42568 licence not read
[7]
asset:data:geo:GSE42568 not downloaded
[8]
asset:data:geo:GSE53752 licence not read
[9]
asset:data:geo:GSE53752 not downloaded
[10]
asset:data:geo:GSE70947 licence not read
[11]
asset:data:geo:GSE70947 not downloaded
[12]
execution.not_run
[13]
method.reader_differs_from_extractor
[14]
review.human_critique
[15]
review.independent_reader
[16]
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]
Limma package in R language was used to analyze the DEGs in BC samples compared with normal samples.[6] Gene integration for the DEGs identified from the 7 datasets was conducted employing RobustRankAggreg.[7]
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:33285689", "kind": "science-record", "revision": 8, "content_hash": "sha256:73c7d107f3854e0eb129ac63457355d914213083ddb8959e4b13e159b99bd6bb", "created_at": "2026-11-01T15:41:18Z", "updated_at": "2026-11-01T22:45:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of candidate biomarkers correlated with the pathogenesis and prognosis of breast cancer via integrated bioinformatics analysis.", "doi": "10.1097/MD.0000000000023153", "pmid": "33285689", "authors": ["Shuyu Liu", "Xinkui Liu", "Jiarui Wu", "Wei Zhou", "Mengwei Ni", "Ziqi Meng", "Shanshan Jia", "Jingyuan Zhang", "Siyu Guo", "Shan Lu", "Yingfei Li"], "journal": "Medicine", "year": 2020, "abstract": "BACKGROUND: This study was carried out to identify potential key genes associated with the pathogenesis and prognosis of breast cancer (BC).\nMETHODS: Seven GEO datasets (GSE24124, GSE32641, GSE36295, GSE42568, GSE53752, GSE70947, GSE109169) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between BC and normal breast tissue samples were screened by an integrated analysis of multiple gene expression profile datasets. Hub genes related to the pathogenesis and prognosis of BC were verified by employing protein-protein interaction (PPI) network.\nRESULTS: Ten hub genes with high degree were identified, including CDK1, CDC20, CCNA2, CCNB1, CCNB2, BUB1, BUB1B, CDCA8, KIF11, and TOP2A. Lastly, the Kaplan-Meier plotter (KM plotter) online database demonstrated that higher expression levels of these genes were related to lower overall survival. Experimental validation showed that all 10 hub genes had the same expression trend as predicted.\nCONCLUSION: The findings of this research would provide some directive significance for further investigating the diagnostic and prognostic biomarkers to facilitate the molecular targeting therapy of BC, which could be used as a new biomarker for diagnosis and to guide the combination medicine of BC.", "claims": [{"id": "claim-method", "statement": "Limma package in R language was used to analyze the DEGs in BC samples compared with normal samples.[6] Gene integration for the DEGs identified from the 7 datasets was conducted employing RobustRankAggreg.[7]", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33285689", "locator": "sections[3] \"Gene expression profile data\" paragraph 2", "quote": "Limma package in R language was used to analyze the DEGs in BC samples compared with normal samples.[6] Gene integration for the DEGs identified from the 7 datasets was conducted employing RobustRankAggreg.[7]"}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analyzed during the current study are publicly available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33285689", "locator": "sections[22] \"fn-group\" paragraph 1", "quote": "The datasets generated during and/or analyzed during the current study are publicly available."}], "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:33285689"], "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:GSE24124"], "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:GSE24124"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33285689", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1097/MD.0000000000023153", "sha256": 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