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pmid:31528121

Prognostic significance of TOP2A in non-small cell lung cancer revealed by bioinformatic analysis.

Wenxia Ma · Bin Wang · Yaping Zhang · Ziyue Wang · Dan Niu · Siyu Chen · Zhirong Zhang · Ningning Shen · Weixia Han · Xiaoqin Zhang · Rong Wei · Chen Wang

Cancer cell international · 2019 doi:10.1186/s12935-019-0956-1

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Experiment

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Data

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title
Prognostic significance of TOP2A in non-small cell lung cancer revealed by bioinformatic analysis.
doi
10.1186/s12935-019-0956-1
pmid
31528121
authors array · 12 items
[0]
Wenxia Ma
[1]
Bin Wang
[2]
Yaping Zhang
[3]
Ziyue Wang
[4]
Dan Niu
[5]
Siyu Chen
[6]
Zhirong Zhang
[7]
Ningning Shen
[8]
Weixia Han
[9]
Xiaoqin Zhang
[10]
Rong Wei
[11]
Chen Wang
journal
Cancer cell international
year
2019
abstract
BACKGROUND: Lung cancer has been a common malignant tumor with a leading cause of morbidity and mortality, current molecular targets are woefully lacking comparing to the highly progressive cancer. The study is designed to identify new prognostic predictors and potential gene targets based on bioinformatic analysis of Gene Expression Omnibus (GEO) database. METHODS: Four cDNA expression profiles GSE19188, GSE101929, GSE18842 and GSE33532 were chosen from GEO database to analyze the differently expressed genes (DEGs) between non-small cell lung cancer (NSCLC) and normal lung tissues. After the DEGs functions were analyzed, the protein-protein interaction network (PPI) of DEGs were constructed, and the core gene in the network which has high connectivity degree with other genes was identified. We analyzed the association of the gene with the development of NSCLC as well as its prognosis. Lastly we explored the conceivable signaling mechanism of the gene regulation during the development of NSCLC. RESULTS: A total of 92 up regulated and 214 down regulated DEGs were shared in four cDNA expression profiles. Based on their PPI network, TOP2A was connected with most of other genes and was selected for further analysis. Kaplan-Meier overall survival analysis (OS) revealed that TOP2A was associated with worse NSCLC patients survival. And both GEPIA analysis and immunohistochemistry experiment (IHC) confirmed that TOP2A was aberrant gain of expression in cancer comparing to normal tissues. The clinical significance of TOP2A and probable signaling pathways it involved in were further explored, and a positive correlation between TOP2A and TPX2 expression was found in lung cancer tissues. CONCLUSION: Using bioinformatic analysis, we revealed that TOP2A could be adopted as a prognostic indicator of NSCLC and it potentially regulate cancer development through co-work with TPX2. However, more detailed experiments are needed to clarify its drug target role in clinical medical use.
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In the study, we used Kaplan–Meier plotter to analyze the correlation between TOP2A gene and NSCLC patients OS, followed by drawing the survival curve.
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In the study, we used Kaplan–Meier plotter to analyze the correlation between TOP2A gene and NSCLC patients OS, followed by drawing the survival curve.
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All data generated or analyzed during this study are included in this published article.
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[97]
GSM835365
[98]
GSM835366
[99]
GSM835367
sample_count
100
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Intratumor heterogeneity of gene expression profiles in early stage non-small cell lung cancer (NSCLC)
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
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[5] object · 16 fields
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The significant changes of TOP2A expression in transcription level between different types of lung cancer and normal tissues (ONCOMINE database)
structure object · 5 fields
pmcid
PMC6737627
section_index
17
section_title
Aberrant TOP2A up regulation in human NSCLC cancer
row_count
11
column_count
6
table object · 8 fields
label
Table 1
caption
The significant changes of TOP2A expression in transcription level between different types of lung cancer and normal tissues (ONCOMINE database)
rows array · 11 items
[0] array · 6 items
[0]
Subtype of lung cancer
[1]
P-value
[2]
Fold change
[3]
Rank (%)
[4]
Sample
[5]
References
[1] array · 6 items
[0]
Lung adenocarcinoma
[1]
1.65E−5
[2]
4.578
[3]
1
[4]
9
[5]
Yamagata
[2] array · 6 items
[0]
Squamous cell lung carcinoma
[1]
2.84E−6
[2]
4.284
[3]
1
[4]
12
[5]
Yamagata
[3] array · 6 items
[0]
Lung adenocarcinoma
[1]
1.13E−19
[2]
11.812
[3]
1
[4]
110
[5]
Hou
[4] array · 6 items
[0]
squamous cell lung carcinoma
[1]
2.34E−38
[2]
23.698
[3]
1
[4]
92
[5]
Hou
[5] array · 6 items
[0]
Large cell lung carcinoma
[1]
6.08E−9
[2]
24.158
[3]
1
[4]
84
[5]
Hou
[6] array · 6 items
[0]
Squamous cell lung carcinoma
[1]
7.26E−9
[2]
35.709
[3]
1
[4]
38
[5]
Bhattacharjee
[7] array · 6 items
[0]
Small cell lung carcinoma
[1]
8.63e−8
[2]
12.935
[3]
1
[4]
23
[5]
Bhattacharjee
[8] array · 6 items
[0]
Lung adenocarcinoma
[1]
2.17E−5
[2]
3.222
[3]
2
[4]
46
[5]
Garber
[9] array · 6 items
[0]
Squamous cell lung carcinoma
[1]
1.53E−6
[2]
4.478
[3]
1
[4]
19
[5]
Garber
[10] array · 6 items
[0]
Large cell lung carcinoma
[1]
3.82E−5
[2]
4.043
[3]
1
[4]
10
[5]
Garber
locator
section[17]/table-wrap[1]#Tab1
[6] object · 16 fields
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asset:table:pmid:31528121:2
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table
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jats-table
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application/vnd.jats.table+json
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section[18]/table-wrap[1]#Tab2
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note
The relationship between TOP2A and NSCLC clinical pathological parameters
structure object · 5 fields
pmcid
PMC6737627
section_index
18
section_title
IHC experiment validation of TOP2A gain of expression
row_count
39
column_count
4
table object · 8 fields
label
Table 2
caption
The relationship between TOP2A and NSCLC clinical pathological parameters
rows array · 39 items
[0] array · 3 items
[0]
Group
[1]
TOP2A
[2]
P value
[1] array · 2 items
[0]
−
[1]
+
[2] array · 1 item
[0]
Histological subtype
[3] array · 4 items
[0]
Adenocarcinoma
[1]
48 (78.7%)
[2]
13 (21.3%)
[3]
P = 0.000
[4] array · 3 items
[0]
Squamous carcinoma
[1]
20 (43.5%)
[2]
26 (56.5%)
[5] array · 1 item
[0]
Gender
[6] array · 4 items
[0]
Male
[1]
35 (51.5%)
[2]
33 (48.5%)
[3]
P = 0.001
[7] array · 3 items
[0]
Female
[1]
33 (84.6%)
[2]
6 (15.4%)
[8] array · 1 item
[0]
Age
[9] array · 4 items
[0]
< 55
[1]
15 (75.0%)
[2]
5 (25.0%)
[3]
P = 0.238
[10] array · 3 items
[0]
≥ 55
[1]
53 (60.9%)
[2]
34 (39.1%)
[11] array · 1 item
[0]
Smoke
[12] array · 4 items
[0]
No
[1]
34 (79.1%)
[2]
9 (20.9%)
[3]
P = 0.006
[13] array · 3 items
[0]
Yes
[1]
34 (53.1%)
[2]
30 (46.9%)
[14] array · 1 item
[0]
Location
[15] array · 4 items
[0]
Upper lobe
[1]
31 (58.5%)
[2]
22 (41.5%)
[3]
P = 0.521
[16] array · 3 items
[0]
Middle lobe
[1]
7 (63.6%)
[2]
4 (36.4%)
[17] array · 3 items
[0]
Lower lobe
[1]
30 (69.8%)
[2]
13 (30.2%)
[18] array · 1 item
[0]
Tumor size
[19] array · 4 items
[0]
< 2 cm
[1]
13 (76.5%)
[2]
4 (23.5%)
[3]
P = 0.228
[20] array · 3 items
[0]
≥ 2 cm
[1]
55 (61.6%)
[2]
35 (38.9%)
[21] array · 1 item
[0]
Differentiation poorly
[22] array · 4 items
[0]
Differentiated
[1]
13 (54.2%)
[2]
11 (45.8%)
[3]
P = 0.182
[23] array · 3 items
[0]
Moderately differentiated
[1]
47 (63.5%)
[2]
27 (36.5%)
[24] array · 3 items
[0]
Well differentiated
[1]
8 (88.9%)
[2]
1 (11.1%)
[25] array · 1 item
[0]
p-Stage
[26] array · 4 items
[0]
I
[1]
22 (64.7%)
[2]
12 (35.3%)
[3]
P = 0.907
[27] array · 3 items
[0]
II
[1]
19 (67.9%)
[2]
9 (32.1%)
[28] array · 3 items
[0]
III
[1]
11 (57.9%)
[2]
8 (42.1%)
[29] array · 3 items
[0]
IV
[1]
16 (61.5%)
[2]
10 (38.5%)
[30] array · 1 item
[0]
Invasion of capsule
[31] array · 4 items
[0]
No
[1]
42 (68.9%)
[2]
19 (31.1%)
[3]
P = 0.190
[32] array · 3 items
[0]
Yes
[1]
26 (56.5%)
[2]
20 (43.5%)
[33] array · 1 item
[0]
Invasion of bronchial stump
[34] array · 4 items
[0]
No
[1]
63 (65.6%)
[2]
33 (34.4%)
[3]
P = 0.188
[35] array · 3 items
[0]
Yes
[1]
5 (45.5%)
[2]
6 (54.5%)
[36] array · 1 item
[0]
LN metastasis
[37] array · 4 items
[0]
−
[1]
46 (62.2%)
[2]
28 (37.8%)
[3]
P = 0.656
[38] array · 3 items
[0]
+
[1]
22 (66.7%)
[2]
11 (33.3%)
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section[18]/table-wrap[1]#Tab2
[7] object · 16 fields
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asset:table:pmid:31528121:3
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jats-table
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section[19]/table-wrap[1]#Tab3
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Cox proportional hazards regression on NSCLC overall survival
structure object · 5 fields
pmcid
PMC6737627
section_index
19
section_title
TCGA data explored independent prognostic indicator value of TOP2A in adenocarcinoma
row_count
10
column_count
7
table object · 8 fields
label
Table 3
caption
Cox proportional hazards regression on NSCLC overall survival
rows array · 10 items
[0] array · 3 items
[0]
Variables
[1]
Lung adenocarcinoma
[2]
Lung squamous cell carcinoma
[1] array · 6 items
[0]
Hazard ratio
[1]
95% CI
[2]
P value
[3]
Hazard ratio
[4]
95% CI
[5]
P value
[2] array · 1 item
[0]
T
[3] array · 7 items
[0]
T1 vs T2 vs T3 vs T4
[1]
1.356
[2]
1.104–1.665
[3]
0.004
[4]
1.275
[5]
0.998–1.630
[6]
0.052
[4] array · 1 item
[0]
N
[5] array · 7 items
[0]
N0 vs N1–3
[1]
1.839
[2]
1.198–2.822
[3]
0.005
[4]
1.097
[5]
0.726–1.657
[6]
0.66
[6] array · 1 item
[0]
M
[7] array · 7 items
[0]
M0 vs M1
[1]
1.031
[2]
0.865–1.229
[3]
0.735
[4]
1.235
[5]
1.017–1.500
[6]
0.033
[8] array · 1 item
[0]
TOP2A expression
[9] array · 7 items
[0]
< median vs > median
[1]
0.663
[2]
0.500–0.879
[3]
0.004
[4]
1.246
[5]
0.914–1.699
[6]
0.064
locator
section[19]/table-wrap[1]#Tab3
[8] object · 16 fields
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asset:table:pmid:31528121:4
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table
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jats-table
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application/vnd.jats.table+json
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section[20]/table-wrap[1]#Tab4
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Biological process events centered on TOP2A
structure object · 5 fields
pmcid
PMC6737627
section_index
20
section_title
TOP2A centered signaling pathways
row_count
6
column_count
5
table object · 8 fields
label
Table 4
caption
Biological process events centered on TOP2A
rows array · 6 items
[0] array · 5 items
[0]
Description
[1]
Counts
[2]
Background gene counts
[3]
FDR
[4]
Matching proteins in the network
[1] array · 5 items
[0]
Mitotic cell cycle
[1]
10
[2]
628
[3]
9.19E−12
[4]
BUB1, CCNB2, CDC20, CDK1, DLGAP5, NCAPG, PBK, TOP2A, TPX2, UBE2C
[2] array · 5 items
[0]
Cell division
[1]
9
[2]
483
[3]
6.67E−11
[4]
BUB1, CCNB2, CDC20, CDK1, NCAPG, TOP1, TOP2A, TPX2, UBE2C
[3] array · 5 items
[0]
Mitotic cell cycle process
[1]
9
[2]
564
[3]
1.76E−10
[4]
BUB1, CCNB2, CDC20, CDK1, DLGAP5, NCAPG, TOP2A, TPX2, UBE2C
[4] array · 5 items
[0]
Nuclear division
[1]
7
[2]
268
[3]
4.29E−09
[4]
BUB1, CDC20, DLGAP5, NCAPG, TOP2A, TPX2, UBE2C
[5] array · 5 items
[0]
Chromosome segregation
[1]
6
[2]
253
[3]
1.89E−07
[4]
BUB1, CDC20, DLGAP5, NCAPG, TOP1, TOP2A
locator
section[20]/table-wrap[1]#Tab4
[9] object · 16 fields
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asset:table:pmid:31528121:5
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table
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jats-table
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application/vnd.jats.table+json
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null
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sha256:b942dbdb59423a3020954188622fbbbb00c8fb1ef3793963fd43ff70fc17c9fa
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read_table
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section[20]/table-wrap[2]#Tab5
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KEGG signaling pathways centered on TOP2A
structure object · 5 fields
pmcid
PMC6737627
section_index
20
section_title
TOP2A centered signaling pathways
row_count
9
column_count
5
table object · 8 fields
label
Table 5
caption
KEGG signaling pathways centered on TOP2A
rows array · 9 items
[0] array · 5 items
[0]
Term description
[1]
Counts
[2]
Background gene counts
[3]
FDR
[4]
Matching proteins in the network
[1] array · 5 items
[0]
Cell cycle
[1]
4
[2]
123
[3]
5.57E−06
[4]
BUB1, CCNB2, CDC20, CDK1
[2] array · 5 items
[0]
Oocyte meiosis
[1]
4
[2]
116
[3]
5.57E−06
[4]
BUB1, CCNB2, CDC20, CDK1
[3] array · 5 items
[0]
Progesterone-mediated oocyte maturation
[1]
3
[2]
94
[3]
8.19E−05
[4]
BUB1, CCNB2, CDK1
[4] array · 5 items
[0]
p53 signaling pathway
[1]
2
[2]
68
[3]
0.0022
[4]
CCNB2, CDK1
[5] array · 5 items
[0]
Ubiquitin mediated proteolysis
[1]
2
[2]
134
[3]
0.0066
[4]
CDC20, UBE2C
[6] array · 5 items
[0]
Cellular senescence
[1]
2
[2]
156
[3]
0.0074
[4]
CCNB2, CDK1
[7] array · 5 items
[0]
Viral carcinogenesis
[1]
2
[2]
183
[3]
0.0086
[4]
CDC20, CDK1
[8] array · 5 items
[0]
HTLV-I infection
[1]
2
[2]
250
[3]
0.0137
[4]
CCNB2, CDC20
locator
section[20]/table-wrap[2]#Tab5
gaps array · 8 items
[0]
asset:data:geo:GSE101929 not downloaded
[1]
asset:data:geo:GSE101929 licence not read
[2]
asset:data:geo:GSE18842 not downloaded
[3]
asset:data:geo:GSE18842 licence not read
[4]
asset:data:geo:GSE19188 not downloaded
[5]
asset:data:geo:GSE19188 licence not read
[6]
asset:data:geo:GSE33532 not downloaded
[7]
asset:data:geo:GSE33532 licence not read
analysis object · 4 fields
state
partial
methods array · 4 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
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[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
0.7
band
medium
quote
Kaplan-Meier
[1] object · 10 fields
id
method-2
family
network_analysis
specific
ppi_network
label
Network / pathway analysis
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[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
[2] object · 10 fields
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method-3
family
contingency_analysis
specific
chi_square
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Categorical (contingency table) analysis
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[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
[3] object · 10 fields
id
method-4
family
null
specific
null
label
Kaplan–Meier survival 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
verbatim
quote
In the study, we used Kaplan–Meier plotter to analyze the correlation between TOP2A gene and NSCLC patients OS, followed by drawing the survival curve.
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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
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
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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 · 4 items
[0]
GSE19188
[1]
GSE101929
[2]
GSE18842
[3]
GSE33532
resolved_accessions array · 4 items
[0]
GSE19188
[1]
GSE101929
[2]
GSE18842
[3]
GSE33532
statements array · 1 item
[0]
All data generated or analyzed during this study are included in this published article.
basis
The paper names GSE19188, GSE101929, GSE18842, GSE33532 in Gene Expression Omnibus (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
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[0]
source:pmid:31528121
[1]
data:geo:GSE101929
[2]
asset:table:pmid:31528121:1
[3]
asset:table:pmid:31528121:2
[4]
asset:table:pmid:31528121:3
[5]
asset:table:pmid:31528121:4
[6]
asset:table:pmid:31528121:5
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[0]
run_analysis
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[0]
data:geo:GSE101929
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review object · 5 fields
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partial
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extraction_review
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MiniMax-M3.1-Flash
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minimax
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minimax
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2026-10-31T18:16:29Z
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single_reader
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verbatim
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verbatim
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30971
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extraction
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MiniMax-M3.1-Flash
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minimax
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review.independent_reader
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review.machine_critique
[2]
review.human_critique
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not_run
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execution.not_run
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pmid:31528121
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pmid:31528121
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source:pmid:31528121
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PMID 31528121 full text
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data:geo:GSE101929
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dataset
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GEO GSE101929
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pmid:31528121
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pmid:31528121
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PMID 31528121 full text
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data:geo:GSE101929
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GEO GSE101929
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agent:corpus-assay-engine
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activity-read-31528121
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extraction
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source:pmid:31528121
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agent:minimax-reader
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data:geo:GSE101929
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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agent:minimax-reader
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343fb30756ba6ec3
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parent_id
pmid:31528121
parent_hash
sha256:4be595a08afba6fa74b8569d0d9713963d4a423e2e78fe32ab531a30082019df
fork_of
null
gaps array · 13 items
[0]
asset:data:geo:GSE101929 licence not read
[1]
asset:data:geo:GSE101929 not downloaded
[2]
asset:data:geo:GSE18842 licence not read
[3]
asset:data:geo:GSE18842 not downloaded
[4]
asset:data:geo:GSE19188 licence not read
[5]
asset:data:geo:GSE19188 not downloaded
[6]
asset:data:geo:GSE33532 licence not read
[7]
asset:data:geo:GSE33532 not downloaded
[8]
execution.not_run
[9]
method.reader_named_unmapped
[10]
review.human_critique
[11]
review.independent_reader
[12]
review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 4 items
[0]
tients survival. And both GEPIA analysis and immunohistochemistry experiment (IHC) confirmed that TOP2A was ab
[1]
nalysis and immunohistochemistry experiment (IHC) confirmed that TOP2A was aberrant gain of e
[2]
TOP2A between NSCLC and normal lung samples. Immunohistochemistry (IHC) experiment regents and tissue samples
[3]
in were from the hospital supply department. Immunohistochemistry (IHC) experiment protocol IHC experiment was
order_basis
paper_text_order:1429
id
assay:1
[1] 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
[0]
Kaplan-Meier
order_basis
consumes_earlier_output
id
assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31528121", "kind": "science-record", "revision": 7, "content_hash": "sha256:00b2232f76e4ba5cd62574f43dbc3d7d5e23aae2aa2722dd0b2a977bc7f272c2", "created_at": "2026-11-01T15:40:49Z", "updated_at": "2026-11-01T22:00:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic significance of TOP2A in non-small cell lung cancer revealed by bioinformatic analysis.", "doi": "10.1186/s12935-019-0956-1", "pmid": "31528121", "authors": ["Wenxia Ma", "Bin Wang", "Yaping Zhang", "Ziyue Wang", "Dan Niu", "Siyu Chen", "Zhirong Zhang", "Ningning Shen", "Weixia Han", "Xiaoqin Zhang", "Rong Wei", "Chen Wang"], "journal": "Cancer cell international", "year": 2019, "abstract": "BACKGROUND: Lung cancer has been a common malignant tumor with a leading cause of morbidity and mortality, current molecular targets are woefully lacking comparing to the highly progressive cancer. The study is designed to identify new prognostic predictors and potential gene targets based on bioinformatic analysis of Gene Expression Omnibus (GEO) database.\nMETHODS: Four cDNA expression profiles GSE19188, GSE101929, GSE18842 and GSE33532 were chosen from GEO database to analyze the differently expressed genes (DEGs) between non-small cell lung cancer (NSCLC) and normal lung tissues. After the DEGs functions were analyzed, the protein-protein interaction network (PPI) of DEGs were constructed, and the core gene in the network which has high connectivity degree with other genes was identified. We analyzed the association of the gene with the development of NSCLC as well as its prognosis. Lastly we explored the conceivable signaling mechanism of the gene regulation during the development of NSCLC.\nRESULTS: A total of 92 up regulated and 214 down regulated DEGs were shared in four cDNA expression profiles. Based on their PPI network, TOP2A was connected with most of other genes and was selected for further analysis. Kaplan-Meier overall survival analysis (OS) revealed that TOP2A was associated with worse NSCLC patients survival. And both GEPIA analysis and immunohistochemistry experiment (IHC) confirmed that TOP2A was aberrant gain of expression in cancer comparing to normal tissues. The clinical significance of TOP2A and probable signaling pathways it involved in were further explored, and a positive correlation between TOP2A and TPX2 expression was found in lung cancer tissues.\nCONCLUSION: Using bioinformatic analysis, we revealed that TOP2A could be adopted as a prognostic indicator of NSCLC and it potentially regulate cancer development through co-work with TPX2. However, more detailed experiments are needed to clarify its drug target role in clinical medical use.", "claims": [{"id": "claim-method", "statement": "In the study, we used Kaplan–Meier plotter to analyze the correlation between TOP2A gene and NSCLC patients OS, followed by drawing the survival curve.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31528121", "locator": "sections[6] \"Kaplan–Meier survival analysis\" paragraph 2", "quote": "In the study, we used Kaplan–Meier plotter to analyze the correlation between TOP2A gene and NSCLC patients OS, followed by drawing the survival curve."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31528121", "locator": "sections[29] \"notes\" paragraph 1", "quote": "All data generated or analyzed during this study are included in this published article."}], "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:31528121"], "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:GSE101929"], "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:GSE101929"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31528121", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-019-0956-1", "sha256": 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{"pmcid": "PMC6737627", "section_index": 17, "section_title": "Aberrant TOP2A up regulation in human NSCLC cancer", "row_count": 11, "column_count": 6}, "table": {"label": "Table 1", "caption": "The significant changes of TOP2A expression in transcription level between different types of lung cancer and normal tissues (ONCOMINE database)", "rows": [["Subtype of lung cancer", "P-value", "Fold change", "Rank (%)", "Sample", "References"], ["Lung adenocarcinoma", "1.65E−5", "4.578", "1", "9", "Yamagata"], ["Squamous cell lung carcinoma", "2.84E−6", "4.284", "1", "12", "Yamagata"], ["Lung adenocarcinoma", "1.13E−19", "11.812", "1", "110", "Hou"], ["squamous cell lung carcinoma", "2.34E−38", "23.698", "1", "92", "Hou"], ["Large cell lung carcinoma", "6.08E−9", "24.158", "1", "84", "Hou"], ["Squamous cell lung carcinoma", "7.26E−9", "35.709", "1", "38", "Bhattacharjee"], ["Small cell lung carcinoma", "8.63e−8", "12.935", "1", "23", "Bhattacharjee"], ["Lung adenocarcinoma", "2.17E−5", "3.222", "2", "46", "Garber"], ["Squamous cell lung carcinoma", "1.53E−6", "4.478", "1", "19", "Garber"], ["Large cell lung carcinoma", "3.82E−5", "4.043", "1", "10", "Garber"]], "row_count": 11, "column_count": 6, "numeric_cells": 40, "header_rows": 1, "locator": "section[17]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:31528121:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1ecbba0ff11a56b06027d037a3e5028c144c70ba1be3bea76160b4df2ee096f2", "bytes": 1567, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#Tab2", "version": null, "note": "The relationship between TOP2A and NSCLC clinical pathological parameters", "structure": {"pmcid": "PMC6737627", "section_index": 18, "section_title": "IHC experiment validation of TOP2A gain of expression", "row_count": 39, "column_count": 4}, "table": {"label": "Table 2", "caption": "The relationship between TOP2A and NSCLC clinical pathological parameters", "rows": [["Group", "TOP2A", "P value"], ["−", "+"], ["Histological subtype"], ["Adenocarcinoma", "48 (78.7%)", "13 (21.3%)", "P = 0.000"], ["Squamous carcinoma", "20 (43.5%)", "26 (56.5%)"], ["Gender"], ["Male", "35 (51.5%)", "33 (48.5%)", "P = 0.001"], ["Female", "33 (84.6%)", "6 (15.4%)"], ["Age"], ["< 55", "15 (75.0%)", "5 (25.0%)", "P = 0.238"], ["≥ 55", "53 (60.9%)", "34 (39.1%)"], ["Smoke"], ["No", "34 (79.1%)", "9 (20.9%)", "P = 0.006"], ["Yes", "34 (53.1%)", "30 (46.9%)"], ["Location"], ["Upper lobe", "31 (58.5%)", "22 (41.5%)", "P = 0.521"], ["Middle lobe", "7 (63.6%)", "4 (36.4%)"], ["Lower lobe", "30 (69.8%)", "13 (30.2%)"], ["Tumor size"], ["< 2 cm", "13 (76.5%)", "4 (23.5%)", "P = 0.228"], ["≥ 2 cm", "55 (61.6%)", "35 (38.9%)"], ["Differentiation poorly"], ["Differentiated", "13 (54.2%)", "11 (45.8%)", "P = 0.182"], ["Moderately differentiated", "47 (63.5%)", "27 (36.5%)"], ["Well differentiated", "8 (88.9%)", "1 (11.1%)"], ["p-Stage"], ["I", "22 (64.7%)", "12 (35.3%)", "P = 0.907"], ["II", "19 (67.9%)", "9 (32.1%)"], ["III", "11 (57.9%)", "8 (42.1%)"], ["IV", "16 (61.5%)", "10 (38.5%)"], ["Invasion of capsule"], ["No", "42 (68.9%)", "19 (31.1%)", "P = 0.190"], ["Yes", "26 (56.5%)", "20 (43.5%)"], ["Invasion of bronchial stump"], ["No", "63 (65.6%)", "33 (34.4%)", "P = 0.188"], ["Yes", "5 (45.5%)", "6 (54.5%)"], ["LN metastasis"], ["−", "46 (62.2%)", "28 (37.8%)", "P = 0.656"], ["+", "22 (66.7%)", "11 (33.3%)"]], "row_count": 39, "column_count": 4, "numeric_cells": 67, "header_rows": 2, "locator": "section[18]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:31528121:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4fe32492dd5ddaf5c024cfa2e36f1e16716b8b3a5aee298138240dbbd3952c5f", "bytes": 723, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[1]#Tab3", "version": null, "note": "Cox proportional hazards regression on NSCLC overall survival", "structure": {"pmcid": "PMC6737627", "section_index": 19, "section_title": "TCGA data explored independent prognostic indicator value of TOP2A in adenocarcinoma", "row_count": 10, "column_count": 7}, "table": {"label": "Table 3", "caption": "Cox proportional hazards regression on NSCLC overall survival", "rows": [["Variables", "Lung adenocarcinoma", "Lung squamous cell carcinoma"], ["Hazard ratio", "95% CI", "P value", "Hazard ratio", "95% CI", "P value"], ["T"], ["T1 vs T2 vs T3 vs T4", "1.356", "1.104–1.665", "0.004", "1.275", "0.998–1.630", "0.052"], ["N"], ["N0 vs N1–3", "1.839", "1.198–2.822", "0.005", "1.097", "0.726–1.657", "0.66"], ["M"], ["M0 vs M1", "1.031", "0.865–1.229", "0.735", "1.235", "1.017–1.500", "0.033"], ["TOP2A expression"], ["< median vs > median", "0.663", "0.500–0.879", "0.004", "1.246", "0.914–1.699", "0.064"]], "row_count": 10, "column_count": 7, "numeric_cells": 27, "header_rows": 2, "locator": "section[19]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:31528121:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d4cb7cbcf01f876c42ba0b4c5fadeefaf07d2b209a06a5ac9a02b4fb85b3cd8d", "bytes": 800, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#Tab4", "version": null, "note": "Biological process events centered on TOP2A", "structure": {"pmcid": "PMC6737627", "section_index": 20, "section_title": "TOP2A centered signaling pathways", "row_count": 6, "column_count": 5}, "table": {"label": "Table 4", "caption": "Biological process events centered on TOP2A", "rows": [["Description", "Counts", "Background gene counts", "FDR", "Matching proteins in the network"], ["Mitotic cell cycle", "10", "628", "9.19E−12", "BUB1, CCNB2, CDC20, CDK1, DLGAP5, NCAPG, PBK, TOP2A, TPX2, UBE2C"], ["Cell division", "9", "483", "6.67E−11", "BUB1, CCNB2, CDC20, CDK1, NCAPG, TOP1, TOP2A, TPX2, UBE2C"], ["Mitotic cell cycle process", "9", "564", "1.76E−10", "BUB1, CCNB2, CDC20, CDK1, DLGAP5, NCAPG, TOP2A, TPX2, UBE2C"], ["Nuclear division", "7", "268", "4.29E−09", "BUB1, CDC20, DLGAP5, NCAPG, TOP2A, TPX2, UBE2C"], ["Chromosome segregation", "6", "253", "1.89E−07", "BUB1, CDC20, DLGAP5, NCAPG, TOP1, TOP2A"]], "row_count": 6, "column_count": 5, "numeric_cells": 20, "header_rows": 1, "locator": "section[20]/table-wrap[1]#Tab4"}}, {"id": "asset:table:pmid:31528121:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b942dbdb59423a3020954188622fbbbb00c8fb1ef3793963fd43ff70fc17c9fa", "bytes": 804, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[2]#Tab5", "version": null, "note": "KEGG signaling pathways centered on TOP2A", "structure": {"pmcid": "PMC6737627", "section_index": 20, "section_title": "TOP2A centered signaling pathways", "row_count": 9, "column_count": 5}, "table": {"label": "Table 5", "caption": "KEGG signaling pathways centered on TOP2A", "rows": [["Term description", "Counts", "Background gene counts", "FDR", "Matching proteins in the network"], ["Cell cycle", "4", "123", "5.57E−06", "BUB1, CCNB2, CDC20, CDK1"], ["Oocyte meiosis", "4", "116", "5.57E−06", "BUB1, CCNB2, CDC20, CDK1"], ["Progesterone-mediated oocyte maturation", "3", "94", "8.19E−05", "BUB1, CCNB2, CDK1"], ["p53 signaling pathway", "2", "68", "0.0022", "CCNB2, CDK1"], ["Ubiquitin mediated proteolysis", "2", "134", "0.0066", "CDC20, UBE2C"], ["Cellular senescence", "2", "156", "0.0074", "CCNB2, CDK1"], ["Viral carcinogenesis", "2", "183", "0.0086", "CDC20, CDK1"], ["HTLV-I infection", "2", "250", "0.0137", "CCNB2, CDC20"]], "row_count": 9, "column_count": 5, "numeric_cells": 30, "header_rows": 1, "locator": 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