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pmid:34322151

Weighted Gene Co-expression Network Analysis Identified a Novel Thirteen-Gene Signature Associated With Progression, Prognosis, and Immune Microenvironment of Colon Adenocarcinoma Patients.

Cangang Zhang · Zhe Zhao · Haibo Liu · Shukun Yao · Dongyan Zhao

Frontiers in genetics · 2021 doi:10.3389/fgene.2021.657658

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title
Weighted Gene Co-expression Network Analysis Identified a Novel Thirteen-Gene Signature Associated With Progression, Prognosis, and Immune Microenvironment of Colon Adenocarcinoma Patients.
doi
10.3389/fgene.2021.657658
pmid
34322151
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Cangang Zhang
[1]
Zhe Zhao
[2]
Haibo Liu
[3]
Shukun Yao
[4]
Dongyan Zhao
journal
Frontiers in genetics
year
2021
abstract
Colon adenocarcinoma (COAD) is one of the most common malignant tumors and has high migration and invasion capacity. In this study, we attempted to establish a multigene signature for predicting the prognosis of COAD patients. Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out. Then, our study employed TCGA-COAD cohort as the training dataset and an independent cohort by merging the GES39582 and GSE17536 datasets as the testing dataset. After univariate and multivariate Cox regression analyses were performed for these overlapping genes and overall survival (OS) of COAD patients in the training dataset, a 13-gene signature was constructed to divide COAD patients into high- and low-risk subgroups with significantly different OS. The testing dataset exhibited the same results utilizing the same predictive signature. The area under the curve of receiver operating characteristic analysis for predicting OS in the training and testing datasets were 0.789 and 0.868, respectively, which revealed the enhanced predictive power of the signature. Multivariate Cox regression analysis further suggested that the 13-gene signature could independently predict OS. Among the 13 prognostic genes, NAT1 and NAT2 were downregulated with deep deletions in tumor tissues in multiple COAD cohorts and exhibited significant correlations with poorer OS based on the GEPIA database. Notably, NAT1 and NAT2 expression levels were positively correlated with infiltrating levels of CD8+ T cells and dendritic cells, exhibiting a foundation for further research investigating the antitumor immune roles played by NAT1 and NAT2 in COAD. Taken together, the results of our study showed that the 13-gene signature could efficiently predict OS and that NAT1 and NAT2 could function as biomarkers for prognosis and the immune response in COAD.
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Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out.
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Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out.
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Publicly available datasets were analyzed in this study. This data can be found here: TCGA repository (http://cancergenome.nih.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/).
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sample_count
585
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null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
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licence_read
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[3] object · 16 fields
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asset:table:pmid:34322151:1
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jats-table
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application/vnd.jats.table+json
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null
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sha256:6b6f042844c669f5732edafea51fee39b5f615a53bd64f532273b1164851eec8
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read_table
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section[16]/table-wrap[1]#T1
version
null
note
Coefficients of 13 genes constituting gene-based risk signature that were identified from multivariate Cox regression analysis.
structure object · 5 fields
pmcid
PMC8312261
section_index
16
section_title
Identification of a Gene-Based Signature From the Training Dataset
row_count
14
column_count
6
table object · 8 fields
label
TABLE 1
caption
Coefficients of 13 genes constituting gene-based risk signature that were identified from multivariate Cox regression analysis.
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[0] array · 6 items
[0]
Gene
[1]
Coefficient
[2]
HR
[3]
HR.95L
[4]
HR.95H
[5]
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[1] array · 6 items
[0]
TSPAN1
[1]
–0.003
[2]
0.997
[3]
0.993
[4]
1.001
[5]
0.140
[2] array · 6 items
[0]
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0.002
[2]
1.002
[3]
1.001
[4]
1.002
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0.001
[3] array · 6 items
[0]
HRCT1
[1]
–0.107
[2]
0.899
[3]
0.768
[4]
1.054
[5]
0.189
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[1]
0.136
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1.146
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1.070
[4]
1.227
[5]
0.001
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[0]
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–0.039
[2]
0.962
[3]
0.915
[4]
1.011
[5]
0.128
[6] array · 6 items
[0]
SLC41A2
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–0.072
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0.931
[3]
0.864
[4]
1.002
[5]
0.06
[7] array · 6 items
[0]
NAT1
[1]
–0.173
[2]
0.841
[3]
0.734
[4]
0.965
[5]
0.014
[8] array · 6 items
[0]
NAT2
[1]
–0.116
[2]
0.890
[3]
0.751
[4]
1.056
[5]
0.181
[9] array · 6 items
[0]
MIER3
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–0.033
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0.968
[3]
0.927
[4]
1.011
[5]
0.138
[10] array · 6 items
[0]
LINC01133
[1]
0.076
[2]
1.079
[3]
1.042
[4]
1.117
[5]
<0.001
[11] array · 6 items
[0]
ZG16
[1]
–0.021
[2]
0.979
[3]
0.960
[4]
0.998
[5]
0.032
[12] array · 6 items
[0]
CHGA
[1]
0.016
[2]
1.016
[3]
1.008
[4]
1.023
[5]
<0.001
[13] array · 6 items
[0]
PPARGC1A
[1]
–0.074
[2]
0.929
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0.851
[4]
1.014
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0.099
locator
section[16]/table-wrap[1]#T1
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Identifying the independent prognostic parameters in the TCGA-COAD dataset.
structure object · 5 fields
pmcid
PMC8312261
section_index
17
section_title
Prognostic Role of the 13-Gene Signature
row_count
9
column_count
7
table object · 8 fields
label
TABLE 2
caption
Identifying the independent prognostic parameters in the TCGA-COAD dataset.
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[0] array · 3 items
[0]
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[1]
Univariable model
[2]
Multivariable model
[1] array · 7 items
[0]
[1]
HR
[2]
95%CI of HR
[3]
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[4]
HR
[5]
95%CI of HR
[6]
P-value
[2] array · 7 items
[0]
13-gene risk score
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1.016
[2]
1.009-1.023
[3]
<0.001
[4]
1.015
[5]
1.008-1.022
[6]
<0.001
[3] array · 7 items
[0]
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[1]
1.016
[2]
0.995-1.037
[3]
0.145
[4]
1.035
[5]
1.013-1.059
[6]
0.002
[4] array · 7 items
[0]
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[1]
1.132
[2]
0.704-1.820
[3]
0.609
[4]
0.968
[5]
0.595-1.573
[6]
0.895
[5] array · 7 items
[0]
AJCC stage
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3.883
[2]
2.309-6.530
[3]
<0.001
[4]
1.993
[5]
0.595-1.573
[6]
0.047
[6] array · 7 items
[0]
ATCC T stage
[1]
7.330
[2]
1.791-29.996
[3]
0.006
[4]
3.163
[5]
0.743-13.475
[6]
0.119
[7] array · 7 items
[0]
AJCC N stage
[1]
4.512
[2]
2.790-7.294
[3]
<0.001
[4]
2.788
[5]
1.590-4.888
[6]
<0.001
[8] array · 7 items
[0]
AJCC M stage
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3.721
[2]
2.300-6.019
[3]
<0.001
[4]
1.598
[5]
0.903-2.829
[6]
0.108
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section[17]/table-wrap[1]#T2
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[0]
asset:data:geo:GSE17536 not downloaded
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asset:data:geo:GSE17536 licence not read
[2]
asset:data:geo:GSE39582 not downloaded
[3]
asset:data:geo:GSE39582 licence not read
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state
partial
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[0] object · 10 fields
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method-1
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survival_analysis
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cox_proportional_hazards
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Survival analysis
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[0]
cox_ph
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parameters object · 0 fields
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[0]
time_to_event_with_censoring
evidence object · 3 fields
score
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medium
quote
Cox regression
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id
method-2
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null
specific
null
label
Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis
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parameters object · 0 fields
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evidence object · 3 fields
score
1
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verbatim
quote
Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out.
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gaps array · 1 item
[0]
method.reader_named_unmapped
capability object · 3 fields
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complete
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[0] object · 6 fields
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capability:computational_analysis
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[0]
meta_analysis
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machine_learning
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survival_analysis
[3]
statistical_regression
[4]
pca
[5]
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[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
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complete
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R1
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nothing:replicable_now
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method object · 5 fields
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R1
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[0]
cox_ph
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: cox_proportional_hazards.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
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The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 2 items
[0]
GSE39582
[1]
GSE17536
resolved_accessions array · 2 items
[0]
GSE39582
[1]
GSE17536
statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. This data can be found here: TCGA repository (http://cancergenome.nih.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/).
basis
The paper names GSE39582, GSE17536 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 · 1 item
[0]
cox_ph
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[0]
source:pmid:34322151
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data:geo:GSE17536
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asset:table:pmid:34322151:1
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[0]
run_analysis
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data:geo:GSE17536
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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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2026-10-31T18:33:08Z
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single_reader
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verbatim
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verbatim
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3
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37457
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12552
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extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.human_critique
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absent
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execution.not_run
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pmid:34322151
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paper
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pmid:34322151
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source:pmid:34322151
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manuscript
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PMID 34322151 full text
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data:geo:GSE17536
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dataset
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GEO GSE17536
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activity-reading-sci-2026-11-01
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classification
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pmid:34322151
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pmid:34322151
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source:pmid:34322151
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PMID 34322151 full text
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data:geo:GSE17536
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GEO GSE17536
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agent:corpus-assay-engine
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agent:minimax-reader
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agent:corpus-assay-engine
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MiniMax literature reader
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reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
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lineage object · 4 fields
parent_id
pmid:34322151
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sha256:ffd2bdde3b23a1239d559592bd329a74f4291baab4c5b5bf5028f71a5a490323
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null
gaps array · 9 items
[0]
asset:data:geo:GSE17536 licence not read
[1]
asset:data:geo:GSE17536 not downloaded
[2]
asset:data:geo:GSE39582 licence not read
[3]
asset:data:geo:GSE39582 not downloaded
[4]
execution.not_run
[5]
method.reader_named_unmapped
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review.human_critique
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review.independent_reader
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review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_id
rna_seq
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
database5 is a web-based tool for analyzing RNA sequencing expression data and providing customizable f
order_basis
paper_text_order:2447
id
assay:1
[1] object · 11 fields
role
analysis
definition_id
survival_analysis
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f2132e96ae6c7a4e
required_operations array · 1 item
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cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
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Cox regression
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:34322151", "kind": "science-record", "revision": 6, "content_hash": "sha256:de80ed195b7e32474d07fd9c22ce158b3350d745275e1c7cd8fa89b8dc450a78", "created_at": "2026-11-01T15:41:45Z", "updated_at": "2026-11-01T21:25:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Weighted Gene Co-expression Network Analysis Identified a Novel Thirteen-Gene Signature Associated With Progression, Prognosis, and Immune Microenvironment of Colon Adenocarcinoma Patients.", "doi": "10.3389/fgene.2021.657658", "pmid": "34322151", "authors": ["Cangang Zhang", "Zhe Zhao", "Haibo Liu", "Shukun Yao", "Dongyan Zhao"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Colon adenocarcinoma (COAD) is one of the most common malignant tumors and has high migration and invasion capacity. In this study, we attempted to establish a multigene signature for predicting the prognosis of COAD patients. Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out. Then, our study employed TCGA-COAD cohort as the training dataset and an independent cohort by merging the GES39582 and GSE17536 datasets as the testing dataset. After univariate and multivariate Cox regression analyses were performed for these overlapping genes and overall survival (OS) of COAD patients in the training dataset, a 13-gene signature was constructed to divide COAD patients into high- and low-risk subgroups with significantly different OS. The testing dataset exhibited the same results utilizing the same predictive signature. The area under the curve of receiver operating characteristic analysis for predicting OS in the training and testing datasets were 0.789 and 0.868, respectively, which revealed the enhanced predictive power of the signature. Multivariate Cox regression analysis further suggested that the 13-gene signature could independently predict OS. Among the 13 prognostic genes, NAT1 and NAT2 were downregulated with deep deletions in tumor tissues in multiple COAD cohorts and exhibited significant correlations with poorer OS based on the GEPIA database. Notably, NAT1 and NAT2 expression levels were positively correlated with infiltrating levels of CD8+ T cells and dendritic cells, exhibiting a foundation for further research investigating the antitumor immune roles played by NAT1 and NAT2 in COAD. Taken together, the results of our study showed that the 13-gene signature could efficiently predict OS and that NAT1 and NAT2 could function as biomarkers for prognosis and the immune response in COAD.", "claims": [{"id": "claim-method", "statement": "Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34322151", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE17536"], "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:GSE17536"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34322151", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.657658", "sha256": "sha256:1606ce9ecbe0e0b5f3686b0051ccc6954eafb7a9464bfd6f89239d12fd1614db", "bytes": 55724, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.657658", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8312261", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17536", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17536", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17536", "version": null, "note": "Publicly available datasets were analyzed in this study. 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