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pmid:33354437

Identification of biomarkers associated with clinical severity of chronic obstructive pulmonary disease.

Jie Zhang · Changli Zhu · Hong Gao · Xun Liang · Xiaoqian Fan · Yulong Zheng · Song Chen · Yufeng Wan

PeerJ · 2020 doi:10.7717/peerj.10513

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complete

Experiment

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Data

partial

Analysis

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absent

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title
Identification of biomarkers associated with clinical severity of chronic obstructive pulmonary disease.
doi
10.7717/peerj.10513
pmid
33354437
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[0]
Jie Zhang
[1]
Changli Zhu
[2]
Hong Gao
[3]
Xun Liang
[4]
Xiaoqian Fan
[5]
Yulong Zheng
[6]
Song Chen
[7]
Yufeng Wan
journal
PeerJ
year
2020
abstract
We sought to identify the biomarkers related to the clinical severity of stage I to stage IV chronic obstructive pulmonary disease (COPD). Gene expression profiles from the blood samples of COPD patients at each of the four stages were acquired from the Gene Expression Omnibus Database (GEO, accession number: GSE54837). Genes showing expression changes among the different stages were sorted by soft clustering. We performed functional enrichment, protein-protein interaction (PPI), and miRNA regulatory network analyses for the differentially expressed genes. The biomarkers associated with the clinical classification of COPD were selected from logistic regression models and the relationships between TLR2 and inflammatory factors were verified in clinical blood samples by qPCR and ELISA. Gene clusters demonstrating continuously rising or falling changes in expression (clusters 1, 2, and 7 and clusters 5, 6, and 8, respectively) from stage I to IV were defined as upregulated and downregulated genes, respectively, and further analyzed. The upregulated genes were enriched in functions associated with defense, inflammatory, or immune responses. The downregulated genes were associated with lymphocyte activation and cell activation. TLR2, HMOX1, and CD79A were hub proteins in the integrated network of PPI and miRNA regulatory networks. TLR2 and CD79A were significantly correlated with clinical classifications. TLR2 was closely associated with inflammatory responses during COPD progression. Functions associated with inflammatory and immune responses as well as lymphocyte activation may play important roles in the progression of COPD from stage I to IV. TLR2 and CD79A may serve as potential biomarkers for the clinical severity of COPD. TLR2 and CD79A may also serve as independent biomarkers in the clinical classification in COPD. TLR2 may play an important role in the inflammatory responses of COPD.
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We analyzed the correlation between TLR2 expression levels and inflammatory factor levels in all detected samples using Pearson Correlation Analysis.
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We analyzed the correlation between TLR2 expression levels and inflammatory factor levels in all detected samples using Pearson Correlation Analysis.
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The following information was supplied regarding data availability:The raw measurements are available in the Supplemental Files.
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Upregulated genes with enriched functions of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG).
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Functional enrichment analyses
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Upregulated genes with enriched functions of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG).
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Influencing factors of the clinical grade of COPD
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[2]
0.2383
[3] array · 3 items
[0]
TLR2
[1]
0.9265
[2]
2.1068E−07***
[4] array · 3 items
[0]
IL-10
[1]
0.3250
[2]
0.1524
[5] array · 3 items
[0]
MMP9
[1]
0.2702
[2]
0.0059**
[6] array · 3 items
[0]
HMOX1
[1]
0.3163
[2]
0.0713
[7] array · 3 items
[0]
CCR1
[1]
0.3503
[2]
0.0298*
[8] array · 3 items
[0]
CD79A
[1]
−0.3443
[2]
0.0002***
[9] array · 3 items
[0]
PLCG1
[1]
−0.7284
[2]
0.0037**
locator
section[17]/table-wrap[1]#table-4
[5] object · 16 fields
id
asset:table:pmid:33354437:4
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table
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jats-table
media_type
application/vnd.jats.table+json
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null
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sha256:86a8ff1d875ab3acc5046ebd670d97fc0085e8413679c5ceffaabda0a45269f9
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414
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read_table
reader_status
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section[17]/table-wrap[2]#table-5
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Results of multivariate logistic regression analysis.
structure object · 5 fields
pmcid
PMC7733647
section_index
9
section_title
Influencing factors of the clinical grade of COPD
row_count
7
column_count
3
table object · 8 fields
label
Table 5
caption
Results of multivariate logistic regression analysis.
rows array · 7 items
[0] array · 3 items
[0]
Factor
[1]
Coefficients
[2]
P value
[1] array · 3 items
[0]
Age
[1]
0.1069
[2]
0.4220
[2] array · 3 items
[0]
TLR2
[1]
0.6894
[2]
0.0027**
[3] array · 3 items
[0]
MMP9
[1]
0.0374
[2]
0.7310
[4] array · 3 items
[0]
CCR1
[1]
0.0282
[2]
0.8695
[5] array · 3 items
[0]
CD79A
[1]
−0.1930
[2]
0.0450*
[6] array · 3 items
[0]
PLCG1
[1]
−0.1267
[2]
0.6488
locator
section[17]/table-wrap[2]#table-5
[6] object · 16 fields
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asset:table:pmid:33354437:5
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table
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jats-table
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section[14]/table-wrap[1]#table-1
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note
Upregulated genes with enriched functions of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG).
structure object · 5 fields
pmcid
PMC7733647
section_index
14
section_title
Functional enrichment analyses
row_count
12
column_count
5
table object · 8 fields
label
Table 1
caption
Upregulated genes with enriched functions of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG).
rows array · 12 items
[0] array · 5 items
[0]
Category
[1]
Term
[2]
Description
[3]
Count
[4]
P value
[1] array · 5 items
[0]
BP
[1]
GO:0006952
[2]
defense response
[3]
22
[4]
3.84E−07
[2] array · 5 items
[0]
BP
[1]
GO:0006954
[2]
inflammatory response
[3]
16
[4]
5.18E−07
[3] array · 5 items
[0]
BP
[1]
GO:0009611
[2]
response to wounding
[3]
20
[4]
7.08E−07
[4] array · 5 items
[0]
BP
[1]
GO:0006955
[2]
immune response
[3]
22
[4]
2.45E−06
[5] array · 5 items
[0]
CC
[1]
GO:0009891
[2]
positive regulation of biosynthetic process
[3]
35
[4]
0.002989929
[6] array · 5 items
[0]
CC
[1]
GO:0051173
[2]
positive regulation of nitrogen compound metabolic process
[3]
22
[4]
0.004929606
[7] array · 5 items
[0]
CC
[1]
GO:0031328
[2]
positive regulation of cellular biosynthetic process
[3]
22
[4]
0.006361208
[8] array · 5 items
[0]
CC
[1]
GO:0045935
[2]
positive regulation of nucleobase, nucleoside, nucleotide, and nucleic acid metabolic process
[3]
51
[4]
0.006484061
[9] array · 5 items
[0]
KEGG
[1]
hsa05322
[2]
Systemic lupus erythematosus
[3]
8
[4]
4.11E−04
[10] array · 5 items
[0]
KEGG
[1]
hsa04620
[2]
Toll-like receptor signaling pathway
[3]
6
[4]
0.012939
[11] array · 5 items
[0]
KEGG
[1]
hsa04060
[2]
Cytokine-cytokine receptor interaction
[3]
9
[4]
0.028464
locator
section[14]/table-wrap[1]#table-1
[7] object · 16 fields
id
asset:table:pmid:33354437:6
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:83d35c6ff3fb15a2b6806d4f5b39a9b1966593bff3090f70c1fc5e3f79ac5a66
bytes
1700
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[14]/table-wrap[2]#table-2
version
null
note
Downregulated genes with enriched functions of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG).
structure object · 5 fields
pmcid
PMC7733647
section_index
14
section_title
Functional enrichment analyses
row_count
23
column_count
5
table object · 8 fields
label
Table 2
caption
Downregulated genes with enriched functions of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG).
rows array · 23 items
[0] array · 5 items
[0]
Category
[1]
Term
[2]
Description
[3]
Count
[4]
P value
[1] array · 5 items
[0]
BP
[1]
GO:0046649
[2]
lymphocyte activation
[3]
11
[4]
1.89E−06
[2] array · 5 items
[0]
BP
[1]
GO:0001775
[2]
cell activation
[3]
12
[4]
7.79E−06
[3] array · 5 items
[0]
BP
[1]
GO:0045321
[2]
leukocyte activation
[3]
11
[4]
1.08E−05
[4] array · 5 items
[0]
BP
[1]
GO:0048534
[2]
lymphoid organ development
[3]
10
[4]
1.19E−04
[5] array · 5 items
[0]
BP
[1]
GO:0002520
[2]
immune system development
[3]
10
[4]
1.87E−04
[6] array · 5 items
[0]
BP
[1]
GO:0030097
[2]
hemopoiesis
[3]
9
[4]
3.33E−04
[7] array · 5 items
[0]
BP
[1]
GO:0030098
[2]
lymphocyte differentiation
[3]
6
[4]
9.42E−04
[8] array · 5 items
[0]
BP
[1]
GO:0042110
[2]
T cell activation
[3]
6
[4]
0.002303352
[9] array · 5 items
[0]
BP
[1]
GO:0002521
[2]
leukocyte differentiation
[3]
6
[4]
0.0027276
[10] array · 5 items
[0]
BP
[1]
GO:0042113
[2]
B cell activation
[3]
4
[4]
0.018182557
[11] array · 5 items
[0]
BP
[1]
GO:0030217
[2]
T cell differentiation
[3]
3
[4]
0.081968615
[12] array · 5 items
[0]
CC
[1]
GO:0009897
[2]
external side of plasma membrane
[3]
4
[4]
0.120963049
[13] array · 5 items
[0]
CC
[1]
GO:0009986
[2]
cell surface
[3]
5
[4]
0.235650749
[14] array · 5 items
[0]
CC
[1]
GO:0044459
[2]
plasma membrane part
[3]
24
[4]
0.033231996
[15] array · 5 items
[0]
CC
[1]
GO:0031226
[2]
intrinsic to plasma membrane
[3]
14
[4]
0.088759042
[16] array · 5 items
[0]
CC
[1]
GO:0005886
[2]
plasma membrane
[3]
34
[4]
0.099440061
[17] array · 5 items
[0]
CC
[1]
GO:0005887
[2]
integral to plasma membrane
[3]
13
[4]
0.136364905
[18] array · 5 items
[0]
KEGG
[1]
hsa04940
[2]
Type I diabetes mellitus
[3]
4
[4]
0.001194
[19] array · 5 items
[0]
KEGG
[1]
hsa04630
[2]
Jak-STAT signaling pathway
[3]
5
[4]
0.007356
[20] array · 5 items
[0]
KEGG
[1]
hsa05330
[2]
Allograft rejection
[3]
3
[4]
0.014236
[21] array · 5 items
[0]
KEGG
[1]
hsa05332
[2]
Graft-versus-host disease
[3]
3
[4]
0.016588
[22] array · 5 items
[0]
KEGG
[1]
hsa04660
[2]
T cell receptor signaling pathway
[3]
4
[4]
0.016985
locator
section[14]/table-wrap[2]#table-2
[8] object · 16 fields
id
asset:table:pmid:33354437:7
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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:fd480d22ca48723281ea8ec7636aa9c5a7546cb25f736de255afacfeaee37235
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1094
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state
verified
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read_table
reader_status
available
identifier
section[15]/table-wrap[1]#table-3
version
null
note
Regulatory microRNAs of gene sets.
structure object · 5 fields
pmcid
PMC7733647
section_index
15
section_title
PPI and miRNA-target gene regulatory relations prediction
row_count
20
column_count
4
table object · 8 fields
label
Table 3
caption
Regulatory microRNAs of gene sets.
rows array · 20 items
[0] array · 4 items
[0]
Sequence
[1]
microRNA
[2]
[3]
Count
[1] array · 4 items
[0]
Hsa-TGGTGCT
[1]
miR-29a, miR-29b, miR-29c
[2]
[3]
6
[2] array · 4 items
[0]
Hsa-AAGGGAT
[1]
miR-188
[2]
[3]
3
[3] array · 4 items
[0]
Hsa-GTGCCTT
[1]
miR-506
[2]
[3]
7
[4] array · 4 items
[0]
Hsa-ACACTAC
[1]
miR-142-3p
[2]
[3]
3
[5] array · 4 items
[0]
Hsa-TGCACTG
[1]
miR-148a, miR-152, miR-148b
[2]
[3]
4
[6] array · 4 items
[0]
Hsa-ACTGAAA
[1]
miR-30a-3p, miR-30e−3p
[2]
[3]
3
[7] array · 4 items
[0]
Hsa-GGGACCA
[1]
miR-133a, miR-133b
[2]
[3]
3
[8] array · 4 items
[0]
Hsa-CTTTGCA
[1]
miR-527
[2]
[3]
3
[9] array · 4 items
[0]
Hsa-CATTTCA
[1]
miR-203
[2]
[3]
3
[10] array · 4 items
[0]
Hsa-TTTGTAG
[1]
miR-520d
[2]
[3]
3
[11] array · 4 items
[0]
Hsa-TAGCTTT
[1]
miR-9
[2]
[3]
4
[12] array · 4 items
[0]
Hsa-AAGCACA
[1]
miR-218
[2]
[3]
4
[13] array · 4 items
[0]
Hsa-TGGTGCT
[1]
miR-29a, miR-29b, miR-29c
[2]
[3]
4
[14] array · 4 items
[0]
Hsa-GCACTTT
[1]
miR-17-5p, miR-20a, miR-106a, miR-106b, miR-20b, miR-519d
[2]
[3]
4
[15] array · 4 items
[0]
Hsa-AAGCCAT
[1]
miR-135a, miR-135b
[2]
[3]
3
[16] array · 4 items
[0]
Hsa-TGCACTT
[1]
miR-519c, miR-519b, miR-519a
[2]
[3]
3
[17] array · 4 items
[0]
Hsa-CTTTGTA,
[1]
miR-524
[2]
[3]
3
[18] array · 4 items
[0]
Hsa-TGAATGT
[1]
miR-181a, miR-181b, miR-181c, miR-181d
[2]
[3]
3
[19] array · 4 items
[0]
Hsa-TGCTGCT
[1]
miR-15a, miR-16, miR-15b, miR-195, miR-424, miR-497
[2]
[3]
3
locator
section[15]/table-wrap[1]#table-3
[9] object · 16 fields
id
asset:table:pmid:33354437:8
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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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sha256:2d0423c074b43469e0005b7c83ada3f301631a156b4b021cf5f1938778d9e9af
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read_table
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section[17]/table-wrap[1]#table-4
version
null
note
Results of univariate logistic regression analysis.
structure object · 5 fields
pmcid
PMC7733647
section_index
17
section_title
Influencing factors of the clinical grade of COPD
row_count
10
column_count
3
table object · 8 fields
label
Table 4
caption
Results of univariate logistic regression analysis.
rows array · 10 items
[0] array · 3 items
[0]
Factor
[1]
Coefficient
[2]
P value
[1] array · 3 items
[0]
Age
[1]
0.2796
[2]
0.0389*
[2] array · 3 items
[0]
Gender
[1]
0.1545
[2]
0.2383
[3] array · 3 items
[0]
TLR2
[1]
0.9265
[2]
2.1068E−07***
[4] array · 3 items
[0]
IL-10
[1]
0.3250
[2]
0.1524
[5] array · 3 items
[0]
MMP9
[1]
0.2702
[2]
0.0059**
[6] array · 3 items
[0]
HMOX1
[1]
0.3163
[2]
0.0713
[7] array · 3 items
[0]
CCR1
[1]
0.3503
[2]
0.0298*
[8] array · 3 items
[0]
CD79A
[1]
−0.3443
[2]
0.0002***
[9] array · 3 items
[0]
PLCG1
[1]
−0.7284
[2]
0.0037**
locator
section[17]/table-wrap[1]#table-4
[10] object · 16 fields
id
asset:table:pmid:33354437:9
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table
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jats-table
media_type
application/vnd.jats.table+json
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null
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sha256:86a8ff1d875ab3acc5046ebd670d97fc0085e8413679c5ceffaabda0a45269f9
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read_table
reader_status
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section[17]/table-wrap[2]#table-5
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note
Results of multivariate logistic regression analysis.
structure object · 5 fields
pmcid
PMC7733647
section_index
17
section_title
Influencing factors of the clinical grade of COPD
row_count
7
column_count
3
table object · 8 fields
label
Table 5
caption
Results of multivariate logistic regression analysis.
rows array · 7 items
[0] array · 3 items
[0]
Factor
[1]
Coefficients
[2]
P value
[1] array · 3 items
[0]
Age
[1]
0.1069
[2]
0.4220
[2] array · 3 items
[0]
TLR2
[1]
0.6894
[2]
0.0027**
[3] array · 3 items
[0]
MMP9
[1]
0.0374
[2]
0.7310
[4] array · 3 items
[0]
CCR1
[1]
0.0282
[2]
0.8695
[5] array · 3 items
[0]
CD79A
[1]
−0.1930
[2]
0.0450*
[6] array · 3 items
[0]
PLCG1
[1]
−0.1267
[2]
0.6488
locator
section[17]/table-wrap[2]#table-5
gaps array · 2 items
[0]
asset:data:geo:GSE54837 not downloaded
[1]
asset:data:geo:GSE54837 licence not read
analysis object · 4 fields
state
partial
methods array · 4 items
[0] object · 10 fields
id
method-1
family
correlation_analysis
specific
pearson
label
Correlation analysis
dsl_operations array · 1 item
[0]
pearson_r
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
1
band
verbatim
quote
We analyzed the correlation between TLR2 expression levels and inflammatory factor levels in all detected samples using Pearson Correlation Analysis.
[1] object · 10 fields
id
method-2
family
group_comparison
specific
anova
label
Group comparison
dsl_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
ANOVA
[2] object · 10 fields
id
method-3
family
regression_modelling
specific
logistic
label
Regression modelling
dsl_operations array · 1 item
[0]
glm_logit_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
predictors_and_outcome
evidence object · 3 fields
score
0.7
band
medium
quote
logistic regression
[3] object · 10 fields
id
method-4
family
network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
protein-protein interaction
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
pearson_r
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: pearson.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 1 item
[0]
GSE54837
resolved_accessions array · 1 item
[0]
GSE54837
statements array · 1 item
[0]
The following information was supplied regarding data availability:The raw measurements are available in the Supplemental Files.
basis
The paper names GSE54837 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]
pearson_r
assets array · 11 items
[0]
source:pmid:33354437
[1]
data:geo:GSE54837
[2]
asset:table:pmid:33354437:1
[3]
asset:table:pmid:33354437:2
[4]
asset:table:pmid:33354437:3
[5]
asset:table:pmid:33354437:4
[6]
asset:table:pmid:33354437:5
[7]
asset:table:pmid:33354437:6
[8]
asset:table:pmid:33354437:7
[9]
asset:table:pmid:33354437:8
[10]
asset:table:pmid:33354437:9
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE54837
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:25:26Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
31218
completion_tokens
1490
cached_tokens
10504
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
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s were verified in clinical blood samples by qPCR and ELISA. Gene clusters demonstrating conti
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We analyzed the correlation between TLR2 expression levels and inflammatory factor levels in all detected samples using Pearson Correlation Analysis.
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Complete file
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