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pmid:36860851

Identification of shared gene signatures and molecular mechanisms between chronic kidney disease and ulcerative colitis.

Zhou Liang · Xinrong Hu · Ruoni Lin · Ziwen Tang · Ziyin Ye · Ren Mao · Wei Chen · Yi Zhou

Frontiers in immunology · 2023 doi:10.3389/fimmu.2023.1078310

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pmid:36860851
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title
Identification of shared gene signatures and molecular mechanisms between chronic kidney disease and ulcerative colitis.
doi
10.3389/fimmu.2023.1078310
pmid
36860851
authors array · 8 items
[0]
Zhou Liang
[1]
Xinrong Hu
[2]
Ruoni Lin
[3]
Ziwen Tang
[4]
Ziyin Ye
[5]
Ren Mao
[6]
Wei Chen
[7]
Yi Zhou
journal
Frontiers in immunology
year
2023
abstract
Background: There is a complex interaction between chronic kidney disease (CKD) and ulcerative colitis (UC), but the pathophysiological mechanisms underlying the coexistence of CKD and UC are unclear. This study aimed to investigate the key molecules and pathways that may mediate the co-occurrence of CKD and UC through quantitative bioinformatics analysis based on a public RNA-sequencing database. Methods: The discovery datasets of CKD (GSE66494) and UC (GSE4183), as well as validation datasets of CKD (GSE115857) and UC (GSE10616), were downloaded from the Gene Expression Omnibus (GEO) database. After identifying differentially expressed genes (DEGs) with GEO2R online tool, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for the DEGs were performed. Next, protein-protein interaction network was constructed with Search Tool for the Retrieval of Interacting Genes (STRING) and visualized by Cytoscape. Gene modules were identified by the plug-in MCODE and hub genes were screened using the plug-in CytoHubba. Then, correlation between immune cell infiltration and hub genes was analyzed, and the receiver operating characteristic curves were used to assess the predictive value of hub genes. Finally, immunostaining of human specimens was used to validate the relevant findings. Results: A total of 462 common DEGs were identified and selected for further analyses. GO and KEGG enrichment analyses indicated that these DEGs were primarily enriched in immune- and inflammation-related pathways. Among them, the PI3K-Akt signaling pathway ranked top in both discovery and validation cohorts, and the key signal molecule phosphorylated Akt (p-Akt) was shown to be significantly overexpressed in human CKD kidneys and UC colons, and further elevated in CKD-UC comorbidity specimens. Moreover, nine candidate hub genes, including CXCL8, CCL2, CD44, ICAM1, IL1A, CXCR2, PTPRC, ITGAX, and CSF3, were identified, of which ICAM1 was validated as a common hub gene. Besides, immune infiltration analysis revealed that neutrophils, macrophages, and CD4+ T memory cells significantly accumulated in both diseases, and ICAM1 was remarkably associated with neutrophil infiltration. Furthermore, intercellular adhesion molecule1 (ICAM1)-mediated neutrophil infiltration was validated to be upregulated in kidney and colon biopsies of CKD and UC patients, and further increased in patients diagnosed with both CKD and UC. Finally, ICAM1 had shown critical value as a diagnostic marker for the co-occurrence of CKD and UC. Conclusions: Our study elucidated that immune response, PI3K-Akt signaling pathway, and ICAM1-mediated neutrophil infiltration might be the common pathogenesis of CKD and UC, and identified ICAM1 as a key potential biomarker and therapeutic target for the comorbidity of these two diseases.
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Differentially expressed genes (DEGs) between diseased group and control group were identified using GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/) online analysis tool based on R packages (GEOquery and Limma).
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sections[4] "Identification of common DEGs in both CKD and UC" paragraph 2
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Differentially expressed genes (DEGs) between diseased group and control group were identified using GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/) online analysis tool based on R packages (GEOquery and Limma).
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The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
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A total of 462 common DEGs were identified and selected for further analyses.
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GSM6044161
[51]
GSM6044162
[52]
GSM6044163
[53]
GSM6044164
[54]
GSM6044165
[55]
GSM6044166
[56]
GSM6044167
[57]
GSM6044168
[58]
GSM6044169
[59]
GSM6044170
[60]
GSM6044171
[61]
GSM6044172
[62]
GSM6044173
[63]
GSM6044174
[64]
GSM6044175
[65]
GSM6044176
[66]
GSM6044177
[67]
GSM6044178
[68]
GSM6044179
[69]
GSM6044180
[70]
GSM6044181
[71]
GSM6044182
[72]
GSM6044183
[73]
GSM6044184
[74]
GSM6044185
[75]
GSM6044186
[76]
GSM6044187
[77]
GSM6044188
[78]
GSM6044189
[79]
GSM6044190
[80]
GSM6044191
[81]
GSM6044192
[82]
GSM6044193
[83]
GSM6044194
[84]
GSM6044195
[85]
GSM6044196
[86]
GSM6044197
[87]
GSM6044198
[88]
GSM6044199
[89]
GSM6044200
[90]
GSM6044201
[91]
GSM6044202
[92]
GSM6044203
[93]
GSM6044204
[94]
GSM6044205
[95]
GSM6044206
[96]
GSM6044207
[97]
GSM6044208
[98]
GSM6044209
[99]
GSM6044210
[100]
GSM6044211
[101]
GSM6044212
[102]
GSM6044213
[103]
GSM6044214
[104]
GSM6044215
[105]
GSM6044216
[106]
GSM6044217
[107]
GSM6044218
[108]
GSM6044219
[109]
GSM6044220
[110]
GSM6044221
[111]
GSM6044222
[112]
GSM6044223
[113]
GSM6044224
[114]
GSM6044225
[115]
GSM6044226
[116]
GSM6044227
[117]
GSM6044228
[118]
GSM6044229
[119]
GSM6044230
[120]
GSM6044231
[121]
GSM6044232
[122]
GSM6044233
[123]
GSM6044234
[124]
GSM6044235
[125]
GSM6044236
[126]
GSM6044237
[127]
GSM6044238
[128]
GSM6044239
[129]
GSM6044240
[130]
GSM6044241
[131]
GSM6044242
[132]
GSM6044243
[133]
GSM6044244
[134]
GSM6044245
[135]
GSM6044246
[136]
GSM6044247
[137]
GSM6044248
[138]
GSM6044249
[139]
GSM6044250
[140]
GSM6044251
[141]
GSM6044252
[142]
GSM6044253
[143]
GSM6044254
[144]
GSM6044255
[145]
GSM6044256
[146]
GSM6044257
[147]
GSM6044258
[148]
GSM6044259
[149]
GSM6044260
[150]
GSM6044261
[151]
GSM6044262
[152]
GSM6044263
[153]
GSM6044264
[154]
GSM6044265
[155]
GSM6044266
[156]
GSM6044267
[157]
GSM6044268
[158]
GSM6044269
[159]
GSM6044270
[160]
GSM6044271
[161]
GSM6044272
[162]
GSM6044273
[163]
GSM6044274
[164]
GSM6044275
[165]
GSM6044276
[166]
GSM6044277
[167]
GSM6044278
[168]
GSM6044279
[169]
GSM6044280
[170]
GSM6044281
[171]
GSM6044282
[172]
GSM6044283
[173]
GSM6044284
[174]
GSM6044285
[175]
GSM6044286
[176]
GSM6044287
[177]
GSM6044288
[178]
GSM6044289
[179]
GSM6044290
[180]
GSM6044291
[181]
GSM6044292
[182]
GSM6044293
[183]
GSM6044294
[184]
GSM6044295
[185]
GSM6044296
[186]
GSM6044297
[187]
GSM6044298
[188]
GSM6044299
[189]
GSM6044300
[190]
GSM6044301
[191]
GSM6044302
[192]
GSM6044303
sample_count
193
group_sizes
null
group_sizes_basis
null
platform
19983
taxon
Homo sapiens
title
Microarray profiles from tubulointerstitial compartment of kidney biopsies from adults screened for enrollment in the NEPTUNE cohort
resolution_checked_at
2026-11-01T18:46:34Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[5] object · 15 fields
id
data:geo:GSE4183
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=GSE4183
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE4183
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
sample_accessions array · 53 items
[0]
GSM95473
[1]
GSM95474
[2]
GSM95475
[3]
GSM95476
[4]
GSM95477
[5]
GSM95478
[6]
GSM95479
[7]
GSM95480
[8]
GSM95481
[9]
GSM95482
[10]
GSM95483
[11]
GSM95484
[12]
GSM95485
[13]
GSM95486
[14]
GSM95487
[15]
GSM95488
[16]
GSM95489
[17]
GSM95490
[18]
GSM95491
[19]
GSM95492
[20]
GSM95493
[21]
GSM95494
[22]
GSM95495
[23]
GSM95496
[24]
GSM95497
[25]
GSM95498
[26]
GSM95499
[27]
GSM95500
[28]
GSM95501
[29]
GSM95502
[30]
GSM95503
[31]
GSM95504
[32]
GSM95505
[33]
GSM95506
[34]
GSM95507
[35]
GSM95508
[36]
GSM95509
[37]
GSM95510
[38]
GSM95511
[39]
GSM95512
[40]
GSM95513
[41]
GSM95514
[42]
GSM95515
[43]
GSM95516
[44]
GSM95517
[45]
GSM95518
[46]
GSM95519
[47]
GSM95520
[48]
GSM95521
[49]
GSM95522
[50]
GSM95523
[51]
GSM95524
[52]
GSM95525
sample_count
53
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[6] object · 15 fields
id
data:geo:GSE47908
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=GSE47908
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE47908
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
sample_accessions array · 60 items
[0]
GSM1162227
[1]
GSM1162228
[2]
GSM1162229
[3]
GSM1162230
[4]
GSM1162231
[5]
GSM1162232
[6]
GSM1162233
[7]
GSM1162234
[8]
GSM1162235
[9]
GSM1162236
[10]
GSM1162237
[11]
GSM1162238
[12]
GSM1162239
[13]
GSM1162240
[14]
GSM1162241
[15]
GSM1162242
[16]
GSM1162243
[17]
GSM1162244
[18]
GSM1162245
[19]
GSM1162246
[20]
GSM1162247
[21]
GSM1162248
[22]
GSM1162249
[23]
GSM1162250
[24]
GSM1162251
[25]
GSM1162252
[26]
GSM1162253
[27]
GSM1162254
[28]
GSM1162255
[29]
GSM1162256
[30]
GSM1162257
[31]
GSM1162258
[32]
GSM1162259
[33]
GSM1162260
[34]
GSM1162261
[35]
GSM1162262
[36]
GSM1162263
[37]
GSM1162264
[38]
GSM1162265
[39]
GSM1162266
[40]
GSM1162267
[41]
GSM1162268
[42]
GSM1162269
[43]
GSM1162270
[44]
GSM1162271
[45]
GSM1162272
[46]
GSM1162273
[47]
GSM1162274
[48]
GSM1162275
[49]
GSM1162276
[50]
GSM1162277
[51]
GSM1162278
[52]
GSM1162279
[53]
GSM1162280
[54]
GSM1162281
[55]
GSM1162282
[56]
GSM1162283
[57]
GSM1162284
[58]
GSM1162285
[59]
GSM1162286
sample_count
60
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Transcriptional analysis of left-sided colitis, pancolitis and ulcerative colitis-associated dysplasia
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[7] object · 15 fields
id
data:geo:GSE66494
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=GSE66494
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE66494
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
sample_accessions array · 61 items
[0]
GSM1623299
[1]
GSM1623300
[2]
GSM1623301
[3]
GSM1623302
[4]
GSM1623303
[5]
GSM1623304
[6]
GSM1623305
[7]
GSM1623306
[8]
GSM1623307
[9]
GSM1623308
[10]
GSM1623309
[11]
GSM1623310
[12]
GSM1623311
[13]
GSM1623312
[14]
GSM1623313
[15]
GSM1623314
[16]
GSM1623315
[17]
GSM1623316
[18]
GSM1623317
[19]
GSM1623318
[20]
GSM1623319
[21]
GSM1623320
[22]
GSM1623321
[23]
GSM1623322
[24]
GSM1623323
[25]
GSM1623324
[26]
GSM1623325
[27]
GSM1623326
[28]
GSM1623327
[29]
GSM1623328
[30]
GSM1623329
[31]
GSM1623330
[32]
GSM1623331
[33]
GSM1623332
[34]
GSM1623333
[35]
GSM1623334
[36]
GSM1623335
[37]
GSM1623336
[38]
GSM1623337
[39]
GSM1623338
[40]
GSM1623339
[41]
GSM1623340
[42]
GSM1623341
[43]
GSM1623342
[44]
GSM1623343
[45]
GSM1623344
[46]
GSM1623345
[47]
GSM1623346
[48]
GSM1623347
[49]
GSM1623348
[50]
GSM1623349
[51]
GSM1623350
[52]
GSM1623351
[53]
GSM1623352
[54]
GSM1623353
[55]
GSM1623354
[56]
GSM1623355
[57]
GSM1623356
[58]
GSM1623357
[59]
GSM1623358
[60]
GSM1623359
sample_count
61
group_sizes
null
group_sizes_basis
null
platform
6480
taxon
Homo sapiens
title
Development of gene expression profiles in human chronic kidney disease
resolution_checked_at
2026-11-01T18:06:44Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[8] object · 15 fields
id
data:geo:GSE87466
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=GSE87466
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE87466
version
null
note
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
sample_accessions array · 108 items
[0]
GSM2332098
[1]
GSM2332099
[2]
GSM2332100
[3]
GSM2332101
[4]
GSM2332102
[5]
GSM2332103
[6]
GSM2332104
[7]
GSM2332105
[8]
GSM2332106
[9]
GSM2332107
[10]
GSM2332108
[11]
GSM2332109
[12]
GSM2332110
[13]
GSM2332111
[14]
GSM2332112
[15]
GSM2332113
[16]
GSM2332114
[17]
GSM2332115
[18]
GSM2332116
[19]
GSM2332117
[20]
GSM2332118
[21]
GSM2332119
[22]
GSM2332120
[23]
GSM2332121
[24]
GSM2332122
[25]
GSM2332123
[26]
GSM2332124
[27]
GSM2332125
[28]
GSM2332126
[29]
GSM2332127
[30]
GSM2332128
[31]
GSM2332129
[32]
GSM2332130
[33]
GSM2332131
[34]
GSM2332132
[35]
GSM2332133
[36]
GSM2332134
[37]
GSM2332135
[38]
GSM2332136
[39]
GSM2332137
[40]
GSM2332138
[41]
GSM2332139
[42]
GSM2332140
[43]
GSM2332141
[44]
GSM2332142
[45]
GSM2332143
[46]
GSM2332144
[47]
GSM2332145
[48]
GSM2332146
[49]
GSM2332147
[50]
GSM2332148
[51]
GSM2332149
[52]
GSM2332150
[53]
GSM2332151
[54]
GSM2332152
[55]
GSM2332153
[56]
GSM2332154
[57]
GSM2332155
[58]
GSM2332156
[59]
GSM2332157
[60]
GSM2332158
[61]
GSM2332159
[62]
GSM2332160
[63]
GSM2332161
[64]
GSM2332162
[65]
GSM2332163
[66]
GSM2332164
[67]
GSM2332165
[68]
GSM2332166
[69]
GSM2332167
[70]
GSM2332168
[71]
GSM2332169
[72]
GSM2332170
[73]
GSM2332171
[74]
GSM2332172
[75]
GSM2332173
[76]
GSM2332174
[77]
GSM2332175
[78]
GSM2332176
[79]
GSM2332177
[80]
GSM2332178
[81]
GSM2332179
[82]
GSM2332180
[83]
GSM2332181
[84]
GSM2332182
[85]
GSM2332183
[86]
GSM2332184
[87]
GSM2332185
[88]
GSM2332186
[89]
GSM2332187
[90]
GSM2332188
[91]
GSM2332189
[92]
GSM2332190
[93]
GSM2332191
[94]
GSM2332192
[95]
GSM2332193
[96]
GSM2332194
[97]
GSM2332195
[98]
GSM2332196
[99]
GSM2332197
[100]
GSM2332198
[101]
GSM2332199
[102]
GSM2332200
[103]
GSM2332201
[104]
GSM2332202
[105]
GSM2332203
[106]
GSM2332204
[107]
GSM2332205
sample_count
108
group_sizes
null
group_sizes_basis
null
platform
13158
taxon
Homo sapiens
title
Gene expression profiling of mucosal biopsies from adult patients with moderately to severely active ulcerative colitis
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 16 items
[0]
asset:data:geo:GSE10616 not downloaded
[1]
asset:data:geo:GSE10616 licence not read
[2]
asset:data:geo:GSE108112 not downloaded
[3]
asset:data:geo:GSE108112 licence not read
[4]
asset:data:geo:GSE115857 not downloaded
[5]
asset:data:geo:GSE115857 licence not read
[6]
asset:data:geo:GSE200818 not downloaded
[7]
asset:data:geo:GSE200818 licence not read
[8]
asset:data:geo:GSE4183 not downloaded
[9]
asset:data:geo:GSE4183 licence not read
[10]
asset:data:geo:GSE47908 not downloaded
[11]
asset:data:geo:GSE47908 licence not read
[12]
asset:data:geo:GSE66494 not downloaded
[13]
asset:data:geo:GSE66494 licence not read
[14]
asset:data:geo:GSE87466 not downloaded
[15]
asset:data:geo:GSE87466 licence not read
analysis object · 4 fields
state
partial
methods array · 6 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
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
Differentially expressed genes (DEGs) between diseased group and control group were identified using GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/) online analysis tool based on R packages (GEOquery and Limma).
[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
analysis of variance
[2] object · 10 fields
id
method-3
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
[3] object · 10 fields
id
method-4
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
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
pathway enrichment
[4] object · 10 fields
id
method-5
family
network_analysis
specific
centrality
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
0.8
band
high
quote
Centrality
[5] object · 10 fields
id
method-6
family
flow_cytometry_analysis
specific
mfi
label
Flow cytometry analysis
dsl_operations array · 3 items
[0]
gate_population
[1]
quantify_mfi
[2]
compensation_matrix
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
event_table
evidence object · 3 fields
score
0.8
band
high
quote
MFI
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]
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The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
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ve bioinformatics analysis based on a public RNA-sequencing database. Methods: The discovery datasets of
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the predictive value of hub genes. Finally, immunostaining of human specimens was used to validate the
[1]
And comparison among more than two groups of immunofluorescence results was assessed by the analysis of vari
[2]
s in the inner circle. (D, E) Representative immunofluorescence staining images of ICAM1 (green) of kidney (
[3]
ing settings as above, and detected ICAM1 by immunofluorescence. As shown in Figures 5D, E, ICAM1 was rarely
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Differentially expressed genes (DEGs) between diseased group and control group were identified using GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/) online analysis tool based on R packages (GEOquery and Limma).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36860851", "kind": "science-record", "revision": 4, "content_hash": "sha256:198fedeac9cbc7fff9d93d5b8ff51341a76000f8b85365630b32efeae36878ab", "created_at": "2026-11-01T19:01:29Z", "updated_at": "2026-11-01T22:51:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of shared gene signatures and molecular mechanisms between chronic kidney disease and ulcerative colitis.", "doi": "10.3389/fimmu.2023.1078310", "pmid": "36860851", "authors": ["Zhou Liang", "Xinrong Hu", "Ruoni Lin", "Ziwen Tang", "Ziyin Ye", "Ren Mao", "Wei Chen", "Yi Zhou"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: There is a complex interaction between chronic kidney disease (CKD) and ulcerative colitis (UC), but the pathophysiological mechanisms underlying the coexistence of CKD and UC are unclear. This study aimed to investigate the key molecules and pathways that may mediate the co-occurrence of CKD and UC through quantitative bioinformatics analysis based on a public RNA-sequencing database.\nMethods: The discovery datasets of CKD (GSE66494) and UC (GSE4183), as well as validation datasets of CKD (GSE115857) and UC (GSE10616), were downloaded from the Gene Expression Omnibus (GEO) database. After identifying differentially expressed genes (DEGs) with GEO2R online tool, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for the DEGs were performed. Next, protein-protein interaction network was constructed with Search Tool for the Retrieval of Interacting Genes (STRING) and visualized by Cytoscape. Gene modules were identified by the plug-in MCODE and hub genes were screened using the plug-in CytoHubba. Then, correlation between immune cell infiltration and hub genes was analyzed, and the receiver operating characteristic curves were used to assess the predictive value of hub genes. Finally, immunostaining of human specimens was used to validate the relevant findings.\nResults: A total of 462 common DEGs were identified and selected for further analyses. GO and KEGG enrichment analyses indicated that these DEGs were primarily enriched in immune- and inflammation-related pathways. Among them, the PI3K-Akt signaling pathway ranked top in both discovery and validation cohorts, and the key signal molecule phosphorylated Akt (p-Akt) was shown to be significantly overexpressed in human CKD kidneys and UC colons, and further elevated in CKD-UC comorbidity specimens. Moreover, nine candidate hub genes, including CXCL8, CCL2, CD44, ICAM1, IL1A, CXCR2, PTPRC, ITGAX, and CSF3, were identified, of which ICAM1 was validated as a common hub gene. Besides, immune infiltration analysis revealed that neutrophils, macrophages, and CD4+ T memory cells significantly accumulated in both diseases, and ICAM1 was remarkably associated with neutrophil infiltration. Furthermore, intercellular adhesion molecule1 (ICAM1)-mediated neutrophil infiltration was validated to be upregulated in kidney and colon biopsies of CKD and UC patients, and further increased in patients diagnosed with both CKD and UC. Finally, ICAM1 had shown critical value as a diagnostic marker for the co-occurrence of CKD and UC.\nConclusions: Our study elucidated that immune response, PI3K-Akt signaling pathway, and ICAM1-mediated neutrophil infiltration might be the common pathogenesis of CKD and UC, and identified ICAM1 as a key potential biomarker and therapeutic target for the comorbidity of these two diseases.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) between diseased group and control group were identified using GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/) online analysis tool based on R packages (GEOquery and Limma).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36860851", "locator": "sections[4] \"Identification of common DEGs in both CKD and UC\" paragraph 2", "quote": "Differentially expressed genes (DEGs) between diseased group and control group were identified using GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/) online analysis tool based on R packages (GEOquery and Limma)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36860851", "locator": "sections[21] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 462 common DEGs were identified and selected for further analyses.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36860851", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 462 common DEGs were identified and selected for further analyses."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 462 common DEGs were identified and selected for further analyses.", "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:36860851"], "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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