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pmid:31724326

A network-based predictive gene expression signature for recurrence risks in stage II colorectal cancer.

Wen-Jing Yang · Hai-Bo Wang · Wen-Da Wang · Peng-Yu Bai · Hong-Xia Lu · Chang-He Sun · Zi-Shen Liu · Ding-Kun Guan · Guo-Wang Yang · Gan-Lin Zhang

Cancer medicine · 2020 doi:10.1002/cam4.2642

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title
A network-based predictive gene expression signature for recurrence risks in stage II colorectal cancer.
doi
10.1002/cam4.2642
pmid
31724326
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Wen-Jing Yang
[1]
Hai-Bo Wang
[2]
Wen-Da Wang
[3]
Peng-Yu Bai
[4]
Hong-Xia Lu
[5]
Chang-He Sun
[6]
Zi-Shen Liu
[7]
Ding-Kun Guan
[8]
Guo-Wang Yang
[9]
Gan-Lin Zhang
journal
Cancer medicine
year
2020
abstract
The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four-gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease-free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein-protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients.
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edgeR is an R package used for the analysis of DEGs10 and was used in our study to screen the DEGs between the recurrence and nonrecurrence groups.
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The datasets used and/or analyzed in current study can be obtained from the corresponding author on reasonable request.
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Inherent gene signature of stage II and III colorectal cancer leads in individual recurrence
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The 18 most significant enriched gene sets for recurrence features of stage II CRC from BP, MF, CC
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The 18 most significant enriched gene sets for recurrence features of stage II CRC from BP, MF, CC
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PMC6943157
section_index
17
section_title
Functional annotation and pathway enrichment analyses
row_count
22
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table object · 8 fields
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Table 3
caption
The 18 most significant enriched gene sets for recurrence features of stage II CRC from BP, MF, CC
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[0] array · 4 items
[0]
ID
[1]
Description
[2]
Count
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P‐Value
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Molecular Function
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GO:0019825
[1]
Oxygen binding
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7
[3]
6.14E‐06
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GO:0005506
[1]
Iron ion binding
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10
[3]
1.96E‐05
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GO:0020037
[1]
Heme binding
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9
[3]
6.04E‐05
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GO:0004497
[1]
Monooxygenase activity
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6
[3]
2.53E‐04
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GO:0016712
[1]
Oxidoreductase activity
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4
[3]
3.83E‐04
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GO:0008395
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Steroid hydroxylase activity
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GO:0004930
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G‐protein coupled receptor activity
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[3]
.00415544
[9] array · 4 items
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GO:0005344
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Oxygen transporter activity
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3
[3]
.00799984
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[0]
GO:0005200
[1]
Structural constituent of cytoskeleton
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5
[3]
.02284408
[11] array · 4 items
[0]
GO:0070330
[1]
Aromatase activity
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3
[3]
.02840488
[12] array · 1 item
[0]
Biological Process
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[0]
GO:0008202
[1]
Steroid metabolic process
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5
[3]
7.68E‐04
[14] array · 4 items
[0]
GO:0015671
[1]
Oxygen transport
[2]
3
[3]
.00894403
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[0]
GO:0007186
[1]
G protein‐coupled receptor signaling pathway
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17
[3]
.01335430
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[0]
GO:0007608
[1]
Sensory perception of smell
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6
[3]
.01900123
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[0]
GO:0017144
[1]
Drug metabolic process
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3
[3]
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GO:0008544
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Epidermis development
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4
[3]
.04905401
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[0]
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[0]
GO:0005833
[1]
Hemoglobin complex
[2]
3
[3]
.00574369
[21] array · 4 items
[0]
GO:0031090
[1]
Organelle membrane
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5
[3]
.01005061
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The 6 most significant enriched pathways for recurrence features of stage II CRC from KEGG
structure object · 5 fields
pmcid
PMC6943157
section_index
17
section_title
Functional annotation and pathway enrichment analyses
row_count
7
column_count
4
table object · 8 fields
label
Table 4
caption
The 6 most significant enriched pathways for recurrence features of stage II CRC from KEGG
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[0] array · 4 items
[0]
KEGG pathway id
[1]
Description
[2]
Count
[3]
P‐Value
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hsa00982
[1]
Drug metabolism—cytochrome P450
[2]
4
[3]
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hsa00983
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Drug metabolism—other enzymes
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4
[3]
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hsa05204
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Chemical carcinogenesis
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5
[3]
.01355137
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hsa00980
[1]
Metabolism of xenobiotics by cytochrome P450
[2]
5
[3]
.0103847
[5] array · 4 items
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hsa00830
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Retinol metabolism
[2]
5
[3]
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[6] array · 4 items
[0]
hsa00140
[1]
Steroid hormone biosynthesis
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8
[3]
4.00E‐06
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The four hub genes in the protein‐protein interaction network
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PMC6943157
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18
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PPI network construction and hub gene identification
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Table 5
caption
The four hub genes in the protein‐protein interaction network
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[0]
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[1]
ATP ‐binding cassette subfamily G member 2
[2]
4.0
[3]
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[1]
Calcium voltage‐gated channel subunit alpha1 F
[2]
4.0
[3]
242.0
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Cytochrome P450 family 19 subfamily A member 1
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10.0
[3]
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Transferrin
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6.0
[3]
680.8
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edgeR is an R package used for the analysis of DEGs10 and was used in our study to screen the DEGs between the recurrence and nonrecurrence groups.
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pathway enrichment
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Automated Assays Laravel application and simulated adapters
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GSE12032
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The datasets used and/or analyzed in current study can be obtained from the corresponding author on reasonable request.
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The paper names GSE12032 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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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31724326", "kind": "science-record", "revision": 8, "content_hash": "sha256:057434ac12270ac3a4b6da6a0ee29c08fc174525169661aed4fd739787740268", "created_at": "2026-11-01T15:40:51Z", "updated_at": "2026-11-01T22:44:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A network-based predictive gene expression signature for recurrence risks in stage II colorectal cancer.", "doi": "10.1002/cam4.2642", "pmid": "31724326", "authors": ["Wen-Jing Yang", "Hai-Bo Wang", "Wen-Da Wang", "Peng-Yu Bai", "Hong-Xia Lu", "Chang-He Sun", "Zi-Shen Liu", "Ding-Kun Guan", "Guo-Wang Yang", "Gan-Lin Zhang"], "journal": "Cancer medicine", "year": 2020, "abstract": "The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four-gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease-free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein-protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients.", "claims": [{"id": "claim-method", "statement": "edgeR is an R package used for the analysis of DEGs10 and was used in our study to screen the DEGs between the recurrence and nonrecurrence groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31724326", "locator": "sections[4] \"Data preprocessing and the identification of DEGs\" paragraph 2", "quote": "edgeR is an R package used for the analysis of DEGs10 and was used in our study to screen the DEGs between the recurrence and nonrecurrence groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed in current study can be obtained from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31724326", "locator": "sections[27] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The datasets used and/or analyzed in current study can be obtained from the corresponding author on reasonable request."}], "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:31724326"], "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. 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