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pmid:31598425

Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods.

Zihao He · Xiaolu Duan · Guohua Zeng

PeerJ · 2019 doi:10.7717/peerj.7872

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Experiment

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Data

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Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods.
doi
10.7717/peerj.7872
pmid
31598425
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[0]
Zihao He
[1]
Xiaolu Duan
[2]
Guohua Zeng
journal
PeerJ
year
2019
abstract
BACKGROUND: Prostate cancer (PCa) is a common urinary malignancy, whose molecular mechanism has not been fully elucidated. We aimed to screen for key genes and biological pathways related to PCa using bioinformatics method. METHODS: Differentially expressed genes (DEGs) were filtered out from the GSE103512 dataset and subjected to the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein-protein interactions (PPI) network was constructed, following by the identification of hub genes. The results of former studies were compared with ours. The relative expression levels of hub genes were examined in The Cancer Genome Atlas (TCGA) and Oncomine public databases. The University of California Santa Cruz Xena online tools were used to study whether the expression of hub genes was correlated with the survival of PCa patients from TCGA cohorts. RESULTS: Totally, 252 (186 upregulated and 66 downregulated) DEGs were identified. GO analysis enriched mainly in "oxidation-reduction process" and "positive regulation of transcription from RNA polymerase II promoter"; KEGG pathway analysis enriched mostly in "metabolic pathways" and "protein digestion and absorption." Kallikrein-related peptidase 3, cadherin 1 (CDH1), Kallikrein-related peptidase 2 (KLK2), forkhead box A1 (FOXA1), and epithelial cell adhesion molecule (EPCAM) were identified as hub genes from the PPI network. CDH1, FOXA1, and EPCAM were validated by other relevant gene expression omnibus datasets. All hub genes were validated by both TCGA and Oncomine except KLK2. Two additional top DEGs (ABCC4 and SLPI) were found to be associated with the prognosis of PCa patients. CONCLUSIONS: This study excavated the key genes and pathways in PCa, which might be biomarkers for diagnosis, prognosis, and potential therapeutic targets.
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The DEGs were filtered using the limma R package (criteria: adjusted P < 0.05 and |log2 fold change| ≥ 1).
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The following information was supplied regarding data availability: Data is available at NCBI GEO: GSE103512.
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Gene expression profiles of breast, colorectal, prostate, and non-small cell lung cancer
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Pathway enrichment analysis of the genes in the top two Modules.
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[3]
P-value
[4]
Genes
[1] array · 5 items
[0]
Module 1
[1]
Adherens junction
[2]
2
[3]
1.0E-2
[4]
CDH1, SNAI2
[2] array · 5 items
[0]
[1]
Hippo signaling pathway
[2]
2
[3]
2.0E-2
[4]
CDH1, SNAI2
[3] array · 5 items
[0]
Module 2
[1]
Fatty acid metabolism
[2]
4
[3]
1.97E-05
[4]
ACSL1, SCD, FASN, ACSL3
[4] array · 5 items
[0]
[1]
Fatty acid biosynthesis
[2]
3
[3]
9.79E-05
[4]
ACSL1, FASN, ACSL3
[5] array · 5 items
[0]
[1]
PPAR signaling pathway
[2]
3
[3]
0.002925067
[4]
ACSL1, SCD, ACSL3
[6] array · 5 items
[0]
[1]
Fatty acid degradation
[2]
2
[3]
0.047850686
[4]
ACSL1, ACSL3
locator
section[12]/table-wrap[2]#table-5
[5] object · 16 fields
id
asset:table:pmid:31598425:4
role
table
format
jats-table
media_type
application/vnd.jats.table+json
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null
sha256
sha256:6c7f584d2a48ab190dc01dce229856be27e0659a4d7d4ad8f770f140aefe856a
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1320
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verified
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read_table
reader_status
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identifier
section[10]/table-wrap[1]#table-1
version
null
note
Top 10 upregulated and downregulated DEGs between PCa and NP tissues.
structure object · 5 fields
pmcid
PMC6779116
section_index
10
section_title
Data processing and screening of DEGs
row_count
21
column_count
4
table object · 8 fields
label
Table 1
caption
Top 10 upregulated and downregulated DEGs between PCa and NP tissues.
rows array · 21 items
[0] array · 4 items
[0]
Gene symbol
[1]
Log2FC
[2]
adj.P.Val
[3]
State
[1] array · 4 items
[0]
NPY
[1]
−3.362711603
[2]
0.000789175
[3]
Upregulated
[2] array · 4 items
[0]
TARP
[1]
−3.206862002
[2]
4.85E-09
[3]
Upregulated
[3] array · 4 items
[0]
OR51E2
[1]
−2.828448822
[2]
7.28E-05
[3]
Upregulated
[4] array · 4 items
[0]
NKX3-1
[1]
−2.528690546
[2]
3.58E-12
[3]
Upregulated
[5] array · 4 items
[0]
MSMB
[1]
−2.517978536
[2]
5.11E-06
[3]
Upregulated
[6] array · 4 items
[0]
ACPP
[1]
−2.474802744
[2]
2.29E-09
[3]
Upregulated
[7] array · 4 items
[0]
SLC45A3
[1]
−2.46284327
[2]
2.66E-08
[3]
Upregulated
[8] array · 4 items
[0]
C15orf21
[1]
−2.327851135
[2]
0.003615423
[3]
Upregulated
[9] array · 4 items
[0]
ABCC4
[1]
−2.261776258
[2]
1.46E-08
[3]
Upregulated
[10] array · 4 items
[0]
LOC100287445
[1]
−2.170028348
[2]
0.000544702
[3]
Upregulated
[11] array · 4 items
[0]
FOLR1
[1]
3.005860886
[2]
8.83E-09
[3]
Downregulated
[12] array · 4 items
[0]
KRT13
[1]
2.958317838
[2]
2.03E-08
[3]
Downregulated
[13] array · 4 items
[0]
SEMG1
[1]
2.881097184
[2]
0.001633121
[3]
Downregulated
[14] array · 4 items
[0]
SEMG2
[1]
2.444264593
[2]
0.00246384
[3]
Downregulated
[15] array · 4 items
[0]
OLFM4
[1]
2.410939695
[2]
0.000494142
[3]
Downregulated
[16] array · 4 items
[0]
SLPI
[1]
2.391184301
[2]
3.98E-05
[3]
Downregulated
[17] array · 4 items
[0]
SCGB1A1
[1]
2.324648206
[2]
2.40E-05
[3]
Downregulated
[18] array · 4 items
[0]
OSR1
[1]
2.028908547
[2]
3.00E-15
[3]
Downregulated
[19] array · 4 items
[0]
HSPB6
[1]
1.791949206
[2]
1.19E-06
[3]
Downregulated
[20] array · 4 items
[0]
CFD
[1]
1.71042558
[2]
1.42E-09
[3]
Downregulated
locator
section[10]/table-wrap[1]#table-1
[6] object · 16 fields
id
asset:table:pmid:31598425:5
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table
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jats-table
media_type
application/vnd.jats.table+json
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null
sha256
sha256:c2d1c932ae8b52931f6764e66a309793cbd2b8101ca7c95bc0082634aa76ace4
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2362
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verified
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read_table
reader_status
available
identifier
section[11]/table-wrap[1]#table-2
version
null
note
Top 15 enriched gene ontology terms of the upregulated and downregulated DEGs.
structure object · 5 fields
pmcid
PMC6779116
section_index
11
section_title
Functional and pathway enrichment analyses of DEGs
row_count
31
column_count
5
table object · 8 fields
label
Table 2
caption
Top 15 enriched gene ontology terms of the upregulated and downregulated DEGs.
rows array · 31 items
[0] array · 5 items
[0]
Category
[1]
Term
[2]
Count
[3]
P-value
[4]
State
[1] array · 5 items
[0]
BP
[1]
Oxidation-reduction process
[2]
17
[3]
1.10E-04
[4]
Upregulated
[2] array · 5 items
[0]
BP
[1]
Proteolysis
[2]
11
[3]
0.01703296
[4]
Upregulated
[3] array · 5 items
[0]
BP
[1]
Long-chain fatty-acyl-CoA biosynthetic process
[2]
6
[3]
3.93E-05
[4]
Upregulated
[4] array · 5 items
[0]
BP
[1]
Response to organic cyclic compound
[2]
4
[3]
0.01023923
[4]
Upregulated
[5] array · 5 items
[0]
BP
[1]
Response to endoplasmic reticulum stress
[2]
4
[3]
0.031611372
[4]
Upregulated
[6] array · 5 items
[0]
CC
[1]
Extracellular exosome
[2]
74
[3]
2.91E-19
[4]
Upregulated
[7] array · 5 items
[0]
CC
[1]
Integral component of membrane
[2]
65
[3]
0.001627446
[4]
Upregulated
[8] array · 5 items
[0]
CC
[1]
Plasma membrane
[2]
56
[3]
7.29E-04
[4]
Upregulated
[9] array · 5 items
[0]
CC
[1]
Membrane
[2]
34
[3]
0.00188457
[4]
Upregulated
[10] array · 5 items
[0]
CC
[1]
Extracellular space
[2]
27
[3]
1.58E-04
[4]
Upregulated
[11] array · 5 items
[0]
MF
[1]
Calcium ion binding
[2]
13
[3]
0.032748281
[4]
Upregulated
[12] array · 5 items
[0]
MF
[1]
Oxidoreductase activity
[2]
9
[3]
5.26E-04
[4]
Upregulated
[13] array · 5 items
[0]
MF
[1]
Actin binding
[2]
9
[3]
0.004195153
[4]
Upregulated
[14] array · 5 items
[0]
MF
[1]
Serine-type peptidase activity
[2]
7
[3]
2.40E-05
[4]
Upregulated
[15] array · 5 items
[0]
MF
[1]
Serine-type endopeptidase activity
[2]
7
[3]
0.030442507
[4]
Upregulated
[16] array · 5 items
[0]
BP
[1]
Positive regulation of transcription from RNA polymerase II promoter
[2]
8
[3]
0.047270726
[4]
Downregulated
[17] array · 5 items
[0]
BP
[1]
Negative regulation of transcription from RNA polymerase II promoter
[2]
7
[3]
0.034624047
[4]
Downregulated
[18] array · 5 items
[0]
BP
[1]
Negative regulation of cell growth
[2]
4
[3]
0.008047189
[4]
Downregulated
[19] array · 5 items
[0]
BP
[1]
Extracellular matrix organization
[2]
4
[3]
0.028910713
[4]
Downregulated
[20] array · 5 items
[0]
BP
[1]
Collagen fibril organization
[2]
3
[3]
0.007739592
[4]
Downregulated
[21] array · 5 items
[0]
CC
[1]
Extracellular exosome
[2]
23
[3]
3.41E-05
[4]
Downregulated
[22] array · 5 items
[0]
CC
[1]
Extracellular space
[2]
20
[3]
2.27E-08
[4]
Downregulated
[23] array · 5 items
[0]
CC
[1]
Extracellular region
[2]
15
[3]
4.96E-04
[4]
Downregulated
[24] array · 5 items
[0]
CC
[1]
Extracellular matrix
[2]
6
[3]
0.002673098
[4]
Downregulated
[25] array · 5 items
[0]
CC
[1]
Blood microparticle
[2]
4
[3]
0.013152355
[4]
Downregulated
[26] array · 5 items
[0]
MF
[1]
Protein binding
[2]
34
[3]
0.021626321
[4]
Downregulated
[27] array · 5 items
[0]
MF
[1]
Drug binding
[2]
4
[3]
0.001392245
[4]
Downregulated
[28] array · 5 items
[0]
MF
[1]
Protein dimerization activity
[2]
4
[3]
0.009398722
[4]
Downregulated
[29] array · 5 items
[0]
MF
[1]
ATPase activity
[2]
4
[3]
0.016027571
[4]
Downregulated
[30] array · 5 items
[0]
MF
[1]
Sodium:potassium-exchanging ATPase activity
[2]
2
[3]
0.028658029
[4]
Downregulated
locator
section[11]/table-wrap[1]#table-2
[7] object · 16 fields
id
asset:table:pmid:31598425:6
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table
format
jats-table
media_type
application/vnd.jats.table+json
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null
sha256
sha256:c4d8aaec196568630371b71253bbecdf69525c5b70487b943479a7a10d95ff15
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1448
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verified
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read_table
reader_status
available
identifier
section[11]/table-wrap[2]#table-3
version
null
note
Top 5 enriched pathways of the upregulated and downregulated DEGs.
structure object · 5 fields
pmcid
PMC6779116
section_index
11
section_title
Functional and pathway enrichment analyses of DEGs
row_count
11
column_count
6
table object · 8 fields
label
Table 3
caption
Top 5 enriched pathways of the upregulated and downregulated DEGs.
rows array · 11 items
[0] array · 6 items
[0]
Pathway ID
[1]
Name
[2]
Count
[3]
P-value
[4]
Genes
[5]
State
[1] array · 6 items
[0]
hsa01100
[1]
Metabolic pathways
[2]
27
[3]
0.001161421
[4]
SAT1, NAMPT, SORD, GCNT2, GALNT7, GLUD1, PPT1, GGT1, ACSL1, ALDH1A3, ARG2, FASN, AMD1, ACSL3, DHCR24, UAP1, ACLY, ADI1, RDH11, FOLH1, ALOX15B, PLA2G7, PLA2G2A, ABAT, MBOAT2, SMS, DCXR
[5]
Upregulated
[2] array · 6 items
[0]
hsa01212
[1]
Fatty acid metabolism
[2]
5
[3]
0.002342524
[4]
ACSL1, SCD, FASN, PPT1, ACSL3
[5]
Upregulated
[3] array · 6 items
[0]
hsa00330
[1]
Arginine and proline metabolism
[2]
4
[3]
0.020729538
[4]
SAT1, ARG2, AMD1, SMS
[5]
Upregulated
[4] array · 6 items
[0]
hsa03320
[1]
PPAR signaling pathway
[2]
4
[3]
0.043990087
[4]
ACSL1, SCD, DBI, ACSL3
[5]
Upregulated
[5] array · 6 items
[0]
hsa00061
[1]
Fatty acid biosynthesis
[2]
3
[3]
0.009820063
[4]
ACSL1, FASN, ACSL3
[5]
Upregulated
[6] array · 6 items
[0]
hsa04974
[1]
Protein digestion and absorption
[2]
3
[3]
0.017282616
[4]
ATP1B1, ATP1A2, COL5A3
[5]
Downregulated
[7] array · 6 items
[0]
hsa04960
[1]
Aldosterone-regulated sodium reabsorption
[2]
2
[3]
0.087044909
[4]
ATP1B1, ATP1A2
[5]
Downregulated
[8] array · 6 items
[0]
hsa04973
[1]
Carbohydrate digestion and absorption
[2]
2
[3]
0.093437569
[4]
ATP1B1, ATP1A2
[5]
Downregulated
[9] array · 6 items
[0]
hsa04978
[1]
Mineral absorption
[2]
2
[3]
0.097676003
[4]
ATP1B1, ATP1A2
[5]
Downregulated
[10] array · 6 items
[0]
hsa04961
[1]
Endocrine and other factor-regulated calcium reabsorption
[2]
2
[3]
0.099788246
[4]
ATP1B1, ATP1A2
[5]
Downregulated
locator
section[11]/table-wrap[2]#table-3
[8] object · 16 fields
id
asset:table:pmid:31598425:7
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:0159f92abafec5d1a133b4930c85db16962c02ef366a31adabcdc3eb8a064808
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618
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read_table
reader_status
available
identifier
section[12]/table-wrap[1]#table-4
version
null
note
Top five hub genes in the protein–protein interaction (PPI) network.
structure object · 5 fields
pmcid
PMC6779116
section_index
12
section_title
PPI network construction and modules analyses
row_count
6
column_count
5
table object · 8 fields
label
Table 4
caption
Top five hub genes in the protein–protein interaction (PPI) network.
rows array · 6 items
[0] array · 5 items
[0]
Gene symbol
[1]
Gene description
[2]
Degree
[3]
Log2FC
[4]
P-Value
[1] array · 5 items
[0]
KLK3
[1]
Kallikrein-related peptidase 3
[2]
26
[3]
2.019308668
[4]
2.04E-11
[2] array · 5 items
[0]
CDH1
[1]
Cadherin 1
[2]
22
[3]
1.21816524
[4]
5.18E-09
[3] array · 5 items
[0]
KLK2
[1]
Kallikrein-related peptidase 2
[2]
21
[3]
1.954704556
[4]
5.64E-11
[4] array · 5 items
[0]
FOXA1
[1]
Forkhead Box A1
[2]
20
[3]
1.922009952
[4]
1.66E-11
[5] array · 5 items
[0]
EPCAM
[1]
Epithelial cell adhesion molecule
[2]
19
[3]
1.076626501
[4]
0.000999371
locator
section[12]/table-wrap[1]#table-4
[9] object · 16 fields
id
asset:table:pmid:31598425:8
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table
format
jats-table
media_type
application/vnd.jats.table+json
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null
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sha256:ac4f2acf4c3182d9f0b902ec30e4cc0eeb28996d83e83ba042e9d19063b9bff2
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658
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read_table
reader_status
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section[12]/table-wrap[2]#table-5
version
null
note
Pathway enrichment analysis of the genes in the top two Modules.
structure object · 5 fields
pmcid
PMC6779116
section_index
12
section_title
PPI network construction and modules analyses
row_count
7
column_count
5
table object · 8 fields
label
Table 5
caption
Pathway enrichment analysis of the genes in the top two Modules.
rows array · 7 items
[0] array · 5 items
[0]
Module
[1]
Pathway
[2]
Count
[3]
P-value
[4]
Genes
[1] array · 5 items
[0]
Module 1
[1]
Adherens junction
[2]
2
[3]
1.0E-2
[4]
CDH1, SNAI2
[2] array · 5 items
[0]
[1]
Hippo signaling pathway
[2]
2
[3]
2.0E-2
[4]
CDH1, SNAI2
[3] array · 5 items
[0]
Module 2
[1]
Fatty acid metabolism
[2]
4
[3]
1.97E-05
[4]
ACSL1, SCD, FASN, ACSL3
[4] array · 5 items
[0]
[1]
Fatty acid biosynthesis
[2]
3
[3]
9.79E-05
[4]
ACSL1, FASN, ACSL3
[5] array · 5 items
[0]
[1]
PPAR signaling pathway
[2]
3
[3]
0.002925067
[4]
ACSL1, SCD, ACSL3
[6] array · 5 items
[0]
[1]
Fatty acid degradation
[2]
2
[3]
0.047850686
[4]
ACSL1, ACSL3
locator
section[12]/table-wrap[2]#table-5
[10] object · 16 fields
id
asset:table:pmid:31598425:9
role
table
format
jats-table
media_type
application/vnd.jats.table+json
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null
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sha256:070b26add7cac411af8d1b4d3bfe07ee4e37a60e585714de02dc937f63685cc6
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1453
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read_table
reader_status
available
identifier
section[13]/table-wrap[1]#table-6
version
null
note
Comparisons between the present study and other studies using the GEO datasets.
structure object · 5 fields
pmcid
PMC6779116
section_index
13
section_title
Validation of hub genes expression in multiple databases
row_count
12
column_count
4
table object · 8 fields
label
Table 6
caption
Comparisons between the present study and other studies using the GEO datasets.
rows array · 12 items
[0] array · 4 items
[0]
Study
[1]
Dataset
[2]
Sample size (PCa, NP)
[3]
Hub genes
[1] array · 4 items
[0]
Endo et al. (2009).
[1]
–
[2]
3, 1
[3]
TSPAN1, BMPR1B, FOXA1, STEAP1, RCAN3, S100P, LYZ, SCGB3A1, IL8, DPT
[2] array · 4 items
[0]
Chen et al. (2012)
[1]
–
[2]
4, 4
[3]
PPFIA2, PTPRT, PTPRR, PRR16, CHRM2, KRT23, CYP3A4, CYP3A7, DPYS, DUOXA1
[3] array · 4 items
[0]
Fang et al. (2017)
[1]
GSE26910
[2]
6, 6
[3]
CDH1, BMP2, NKX3-1, PPARG, PRKAR2B
[4] array · 4 items
[0]
Zhao et al. (2017)
[1]
GSE38241, GSE3933
[2]
47, 37
[3]
CDCA8, CDCA5, UBE2C, TK1
[5] array · 4 items
[0]
Fan et al. (2018)
[1]
GSE55945
[2]
18, 8
[3]
RPS21, FOXO1, BIRC5, POLR2H, RPL22L1, NPM1
[6] array · 4 items
[0]
He et al. (2018)
[1]
GSE46602
[2]
36, 14
[3]
PIK3R1, BIRC5, ITGB4, RRM2, TOP2A, ANXA1, LPAR1, ITGB8
[7] array · 4 items
[0]
Lu & Ding (2019)
[1]
GSE32448, GSE45016, GSE46602, GSE104749
[2]
90, 59
[3]
EPCAM, TWIST1, CD38, VEGFA
[8] array · 4 items
[0]
Song et al. (2019b)
[1]
GSE6919, GSE6956, GSE32448, GSE32571, GSE35988, GSE46602, GSE68555, GSE69223, GSE70768, GSE88808
[2]
569, 402
[3]
LMNB1, TK1, RACGAP1, ZWINT
[9] array · 4 items
[0]
Tan, Jin & Wang (2019)
[1]
GSE38240, GSE26910
[2]
14, 10
[3]
IGF2, GATA5, F10, CFI, AGTR1, FOXA1, BZRAP1-AS1, KRT8
[10] array · 4 items
[0]
Tong, Song & Deng (2019)
[1]
GSE26910, GSE30174, GSE46602, GSE55945, GSE69223
[2]
140, 53
[3]
IKZF1, PPM1A, FBP1, SMCHD1, ALPL, CASP5, PYHIN1, DAPK1, CASP8
[11] array · 4 items
[0]
The present study
[1]
GSE103512
[2]
60, 7
[3]
KLK3, CDH1, KLK2, FOXA1, EPCAM
locator
section[13]/table-wrap[1]#table-6
gaps array · 2 items
[0]
asset:data:geo:GSE103512 not downloaded
[1]
asset:data:geo:GSE103512 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
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The DEGs were filtered using the limma R package (criteria: adjusted P < 0.05 and |log2 fold change| ≥ 1).
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evidence object · 3 fields
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PPI
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capability object · 3 fields
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complete
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Automated Assays Laravel application and simulated adapters
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capability object · 4 fields
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The following information was supplied regarding data availability: Data is available at NCBI GEO: GSE103512.
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The paper names GSE103512 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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ata processing and screening of DEGs The PCa microarray expression dataset GSE103512 contained infor
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The DEGs were filtered using the limma R package (criteria: adjusted P < 0.05 and |log2 fold change| ≥ 1).
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31598425", "kind": "science-record", "revision": 8, "content_hash": "sha256:4e9c9b6c1cf7135aad9f03e87f8456d2294381cb81b586eea87b647574b87147", "created_at": "2026-11-01T15:40:50Z", "updated_at": "2026-11-01T22:44:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods.", "doi": "10.7717/peerj.7872", "pmid": "31598425", "authors": ["Zihao He", "Xiaolu Duan", "Guohua Zeng"], "journal": "PeerJ", "year": 2019, "abstract": "BACKGROUND: Prostate cancer (PCa) is a common urinary malignancy, whose molecular mechanism has not been fully elucidated. We aimed to screen for key genes and biological pathways related to PCa using bioinformatics method.\nMETHODS: Differentially expressed genes (DEGs) were filtered out from the GSE103512 dataset and subjected to the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein-protein interactions (PPI) network was constructed, following by the identification of hub genes. The results of former studies were compared with ours. The relative expression levels of hub genes were examined in The Cancer Genome Atlas (TCGA) and Oncomine public databases. The University of California Santa Cruz Xena online tools were used to study whether the expression of hub genes was correlated with the survival of PCa patients from TCGA cohorts.\nRESULTS: Totally, 252 (186 upregulated and 66 downregulated) DEGs were identified. GO analysis enriched mainly in \"oxidation-reduction process\" and \"positive regulation of transcription from RNA polymerase II promoter\"; KEGG pathway analysis enriched mostly in \"metabolic pathways\" and \"protein digestion and absorption.\" Kallikrein-related peptidase 3, cadherin 1 (CDH1), Kallikrein-related peptidase 2 (KLK2), forkhead box A1 (FOXA1), and epithelial cell adhesion molecule (EPCAM) were identified as hub genes from the PPI network. CDH1, FOXA1, and EPCAM were validated by other relevant gene expression omnibus datasets. All hub genes were validated by both TCGA and Oncomine except KLK2. Two additional top DEGs (ABCC4 and SLPI) were found to be associated with the prognosis of PCa patients.\nCONCLUSIONS: This study excavated the key genes and pathways in PCa, which might be biomarkers for diagnosis, prognosis, and potential therapeutic targets.", "claims": [{"id": "claim-method", "statement": "The DEGs were filtered using the limma R package (criteria: adjusted P < 0.05 and |log2 fold change| ≥ 1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31598425", "locator": "sections[10] \"Data processing and screening of DEGs\" paragraph 2", "quote": "The DEGs were filtered using the limma R package (criteria: adjusted P < 0.05 and |log2 fold change| ≥ 1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nData is available at NCBI GEO: GSE103512.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31598425", "locator": "sections[27] \"Data Availability Statement\" paragraphs 1-3", "quote": "The following information was supplied regarding data availability:\nData is available at NCBI GEO: GSE103512."}], "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:31598425"], "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:GSE103512"], "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:GSE103512"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31598425", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.7872", "sha256": 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{"label": "Table 1", "caption": "Top 10 upregulated and downregulated DEGs between PCa and NP tissues.", "rows": [["Gene symbol", "Log2FC", "adj.P.Val", "State"], ["NPY", "−3.362711603", "0.000789175", "Upregulated"], ["TARP", "−3.206862002", "4.85E-09", "Upregulated"], ["OR51E2", "−2.828448822", "7.28E-05", "Upregulated"], ["NKX3-1", "−2.528690546", "3.58E-12", "Upregulated"], ["MSMB", "−2.517978536", "5.11E-06", "Upregulated"], ["ACPP", "−2.474802744", "2.29E-09", "Upregulated"], ["SLC45A3", "−2.46284327", "2.66E-08", "Upregulated"], ["C15orf21", "−2.327851135", "0.003615423", "Upregulated"], ["ABCC4", "−2.261776258", "1.46E-08", "Upregulated"], ["LOC100287445", "−2.170028348", "0.000544702", "Upregulated"], ["FOLR1", "3.005860886", "8.83E-09", "Downregulated"], ["KRT13", "2.958317838", "2.03E-08", "Downregulated"], ["SEMG1", "2.881097184", "0.001633121", "Downregulated"], ["SEMG2", "2.444264593", "0.00246384", "Downregulated"], ["OLFM4", "2.410939695", "0.000494142", "Downregulated"], ["SLPI", "2.391184301", "3.98E-05", "Downregulated"], ["SCGB1A1", "2.324648206", "2.40E-05", "Downregulated"], ["OSR1", "2.028908547", "3.00E-15", "Downregulated"], ["HSPB6", "1.791949206", "1.19E-06", "Downregulated"], ["CFD", "1.71042558", "1.42E-09", "Downregulated"]], "row_count": 21, "column_count": 4, "numeric_cells": 46, "header_rows": 1, "locator": "section[10]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:31598425:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c2d1c932ae8b52931f6764e66a309793cbd2b8101ca7c95bc0082634aa76ace4", "bytes": 2362, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#table-2", "version": null, "note": "Top 15 enriched gene ontology terms of the upregulated and downregulated DEGs.", "structure": {"pmcid": "PMC6779116", "section_index": 11, "section_title": "Functional and pathway enrichment analyses of DEGs", "row_count": 31, "column_count": 5}, "table": {"label": "Table 2", "caption": "Top 15 enriched gene ontology terms of the upregulated and downregulated DEGs.", "rows": [["Category", "Term", "Count", "P-value", "State"], ["BP", "Oxidation-reduction process", "17", "1.10E-04", "Upregulated"], ["BP", "Proteolysis", "11", "0.01703296", "Upregulated"], ["BP", "Long-chain fatty-acyl-CoA biosynthetic process", "6", "3.93E-05", "Upregulated"], ["BP", "Response to organic cyclic compound", "4", "0.01023923", "Upregulated"], ["BP", "Response to endoplasmic reticulum stress", "4", "0.031611372", "Upregulated"], ["CC", "Extracellular exosome", "74", "2.91E-19", "Upregulated"], ["CC", "Integral component of membrane", "65", "0.001627446", "Upregulated"], ["CC", "Plasma membrane", "56", "7.29E-04", "Upregulated"], ["CC", "Membrane", "34", "0.00188457", "Upregulated"], ["CC", "Extracellular space", "27", "1.58E-04", "Upregulated"], ["MF", "Calcium ion binding", "13", "0.032748281", "Upregulated"], ["MF", "Oxidoreductase activity", "9", "5.26E-04", "Upregulated"], ["MF", "Actin binding", "9", "0.004195153", "Upregulated"], ["MF", "Serine-type peptidase activity", "7", "2.40E-05", "Upregulated"], ["MF", "Serine-type endopeptidase activity", "7", "0.030442507", "Upregulated"], ["BP", "Positive regulation of transcription from RNA polymerase II promoter", "8", "0.047270726", "Downregulated"], ["BP", "Negative regulation of transcription from RNA polymerase II promoter", "7", "0.034624047", "Downregulated"], ["BP", "Negative regulation of cell growth", "4", "0.008047189", "Downregulated"], ["BP", "Extracellular matrix organization", "4", "0.028910713", "Downregulated"], ["BP", "Collagen fibril organization", "3", "0.007739592", "Downregulated"], ["CC", "Extracellular exosome", "23", "3.41E-05", "Downregulated"], ["CC", "Extracellular space", "20", "2.27E-08", "Downregulated"], ["CC", "Extracellular region", "15", "4.96E-04", "Downregulated"], 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"section[11]/table-wrap[2]#table-3", "version": null, "note": "Top 5 enriched pathways of the upregulated and downregulated DEGs.", "structure": {"pmcid": "PMC6779116", "section_index": 11, "section_title": "Functional and pathway enrichment analyses of DEGs", "row_count": 11, "column_count": 6}, "table": {"label": "Table 3", "caption": "Top 5 enriched pathways of the upregulated and downregulated DEGs.", "rows": [["Pathway ID", "Name", "Count", "P-value", "Genes", "State"], ["hsa01100", "Metabolic pathways", "27", "0.001161421", "SAT1, NAMPT, SORD, GCNT2, GALNT7, GLUD1, PPT1, GGT1, ACSL1, ALDH1A3, ARG2, FASN, AMD1, ACSL3, DHCR24, UAP1, ACLY, ADI1, RDH11, FOLH1, ALOX15B, PLA2G7, PLA2G2A, ABAT, MBOAT2, SMS, DCXR", "Upregulated"], ["hsa01212", "Fatty acid metabolism", "5", "0.002342524", "ACSL1, SCD, FASN, PPT1, ACSL3", "Upregulated"], ["hsa00330", "Arginine and proline metabolism", "4", "0.020729538", "SAT1, ARG2, AMD1, SMS", "Upregulated"], ["hsa03320", "PPAR signaling pathway", "4", "0.043990087", "ACSL1, SCD, DBI, ACSL3", "Upregulated"], ["hsa00061", "Fatty acid biosynthesis", "3", "0.009820063", "ACSL1, FASN, ACSL3", "Upregulated"], ["hsa04974", "Protein digestion and absorption", "3", "0.017282616", "ATP1B1, ATP1A2, COL5A3", "Downregulated"], ["hsa04960", "Aldosterone-regulated sodium reabsorption", "2", "0.087044909", "ATP1B1, ATP1A2", "Downregulated"], ["hsa04973", "Carbohydrate digestion and absorption", "2", "0.093437569", "ATP1B1, ATP1A2", "Downregulated"], ["hsa04978", "Mineral absorption", "2", "0.097676003", "ATP1B1, ATP1A2", "Downregulated"], ["hsa04961", "Endocrine and other factor-regulated calcium reabsorption", "2", "0.099788246", "ATP1B1, ATP1A2", "Downregulated"]], "row_count": 11, "column_count": 6, "numeric_cells": 31, "header_rows": 1, "locator": "section[11]/table-wrap[2]#table-3"}}, {"id": "asset:table:pmid:31598425:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": 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junction", "2", "1.0E-2", "CDH1, SNAI2"], ["", "Hippo signaling pathway", "2", "2.0E-2", "CDH1, SNAI2"], ["Module 2", "Fatty acid metabolism", "4", "1.97E-05", "ACSL1, SCD, FASN, ACSL3"], ["", "Fatty acid biosynthesis", "3", "9.79E-05", "ACSL1, FASN, ACSL3"], ["", "PPAR signaling pathway", "3", "0.002925067", "ACSL1, SCD, ACSL3"], ["", "Fatty acid degradation", "2", "0.047850686", "ACSL1, ACSL3"]], "row_count": 7, "column_count": 5, "numeric_cells": 14, "header_rows": 1, "locator": "section[12]/table-wrap[2]#table-5"}}, {"id": "asset:table:pmid:31598425:9", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:070b26add7cac411af8d1b4d3bfe07ee4e37a60e585714de02dc937f63685cc6", "bytes": 1453, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#table-6", "version": null, "note": "Comparisons between the present study and other studies using the GEO datasets.", "structure": {"pmcid": "PMC6779116", "section_index": 13, "section_title": "Validation of hub genes expression in multiple databases", "row_count": 12, "column_count": 4}, "table": {"label": "Table 6", "caption": "Comparisons between the present study and other studies using the GEO datasets.", "rows": [["Study", "Dataset", "Sample size (PCa, NP)", "Hub genes"], ["Endo et al. (2009).", "–", "3, 1", "TSPAN1, BMPR1B, FOXA1, STEAP1, RCAN3, S100P, LYZ, SCGB3A1, IL8, DPT"], ["Chen et al. (2012)", "–", "4, 4", "PPFIA2, PTPRT, PTPRR, PRR16, CHRM2, KRT23, CYP3A4, CYP3A7, DPYS, DUOXA1"], ["Fang et al. (2017)", "GSE26910", "6, 6", "CDH1, BMP2, NKX3-1, PPARG, PRKAR2B"], ["Zhao et al. (2017)", "GSE38241, GSE3933", "47, 37", "CDCA8, CDCA5, UBE2C, TK1"], ["Fan et al. (2018)", "GSE55945", "18, 8", "RPS21, FOXO1, BIRC5, POLR2H, RPL22L1, NPM1"], ["He et al. (2018)", "GSE46602", "36, 14", "PIK3R1, BIRC5, ITGB4, RRM2, TOP2A, ANXA1, LPAR1, ITGB8"], ["Lu & Ding (2019)", "GSE32448, GSE45016, GSE46602, GSE104749", "90, 59", "EPCAM, TWIST1, CD38, VEGFA"], ["Song et al. 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