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pmid:32949121

Prognostic Value of SLC4A4 and its Correlation with Immune Infiltration in Colon Adenocarcinoma.

Xiaoli Chen · Jianing Chen · Yan Feng · Wei Guan

Medical science monitor : international medical journal of experimental and clinical research · 2020 doi:10.12659/MSM.925016

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complete

Experiment

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Data

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Analysis

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title
Prognostic Value of SLC4A4 and its Correlation with Immune Infiltration in Colon Adenocarcinoma.
doi
10.12659/MSM.925016
pmid
32949121
authors array · 4 items
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Xiaoli Chen
[1]
Jianing Chen
[2]
Yan Feng
[3]
Wei Guan
journal
Medical science monitor : international medical journal of experimental and clinical research
year
2020
abstract
BACKGROUND SLC4A4 is differentially expressed in a variety of tumors, but its significance in colon adenocarcinoma has not been determined. MATERIAL AND METHODS Transcriptomes of two cohorts, GSE41258 and GSE32323, contained in The Cancer Genome Atlas (TCGA) were analysed to determine differences in SLC4A4 expression between tumor and normal tissue and their correlations with overall survival. The relationships between SLC4A4 expression and clinical characteristics were determined by COX regression analysis and logistic regression analysis, and correlations of SLC4A4 levels with tumor infiltrating immune cells (TIICs) and genes with high mutation frequency were evaluated by Pearson correlation analysis. Molecular functions and signaling pathways that might be affected by changes in SLC4A4 expression were determined by gene set enrichment analysis (GSEA). The overall distribution of TIICs was determined by two web servers: tumor immune estimation resource (TIMER) and CIBERSORT. RESULTS SLC4A4 expression was lower in colon adenocarcinoma than in normal colon tissue, suggesting that SLC4A4 was associated with poor prognosis. Reduced SLC4A4 expression was also associated with lymph node invasion and distant metastasis and was moderately correlated with increased expression of MUC4 and SMAD4, two genes with high mutation frequency in colon adenocarcinoma. GSEA indicated that changes in SLC4A4 expression affects several biological processes, including mismatch repair, base excision repair, and DNA replication. Eight TIICs in the tumor microenvironment differed significantly in groups with low and high expression of SLC4A4. CONCLUSIONS SLC4A4 may be a novel biomarker predicting prognosis in patients with colon adenocarcinoma. TIICs differed significantly in samples with higher and lower expression of SLC4A4.
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The Mann-Whitney U test was performed to determine whether TIICs belong to different groups.
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Sequencing data on colon adenocarcinomas and corresponding clinical information in the TCGA were downloaded from the UCSC Xena database (https://xenabrowser.net/datapages/) [21], with org.Hs.eg.db (R package) used to annotate Ensembl ID.
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Sequencing data on colon adenocarcinomas and corresponding clinical information in the TCGA were downloaded from the UCSC Xena database (https://xenabrowser.net/datapages/) [21], with org.Hs.eg.db (R package) used to annotate Ensembl ID.
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jats-table
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application/vnd.jats.table+json
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null
sha256
sha256:9d5aa2131c4b1eeb6dbfdc253d681c1e69ef2fa7bbfc06dec0379879e7c7b289
bytes
1662
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[11]/table-wrap[1]#t1-medscimonit-26-e925016
version
null
note
The detailed information of GSEA.
structure object · 5 fields
pmcid
PMC7526338
section_index
11
section_title
Results of functional enrichment analysis
row_count
21
column_count
5
table object · 8 fields
label
Table 1
caption
The detailed information of GSEA.
rows array · 21 items
[0] array · 5 items
[0]
[1]
ID
[2]
Description
[3]
NES
[4]
FDR
[1] array · 5 items
[0]
GO positive
[1]
GO: 0034427
[2]
Nuclear-transcribed mRNA catabolic process, exonucleolytic, 3′-5′
[3]
1.887
[4]
0.022
[2] array · 4 items
[0]
GO: 1902101
[1]
Positive regulation of metaphase/anaphase transition of cell cycle
[2]
1.892
[3]
0.022
[3] array · 4 items
[0]
GO: 1903405
[1]
Protein localization to nuclear body
[2]
1.918
[3]
0.022
[4] array · 4 items
[0]
GO: 1904851
[1]
Positive regulation of establishment of protein localization to telomere
[2]
1.918
[3]
0.022
[5] array · 4 items
[0]
GO: 1904867
[1]
Protein localization to Cajal body
[2]
1.918
[3]
0.022
[6] array · 5 items
[0]
GO negative
[1]
GO: 0007268
[2]
Chemical synaptic transmission
[3]
−1.466
[4]
0.007
[7] array · 4 items
[0]
GO: 0099537
[1]
Trans-synaptic signaling
[2]
−1.468
[3]
0.007
[8] array · 4 items
[0]
GO: 0001508
[1]
Action potential
[2]
−1.492
[3]
0.007
[9] array · 4 items
[0]
GO: 0060078
[1]
Regulation of postsynaptic membrane potential
[2]
−1.509
[3]
0.007
[10] array · 4 items
[0]
GO: 0017158
[1]
Regulation of calcium ion-dependent exocytosis
[2]
−1.512
[3]
0.007
[11] array · 5 items
[0]
KEGG positive
[1]
hsa00100
[2]
Steroid biosynthesis
[3]
2.066
[4]
0.024
[12] array · 4 items
[0]
hsa03430
[1]
Mismatch repair
[2]
2.028
[3]
0.027
[13] array · 4 items
[0]
hsa03410
[1]
Base excision repair
[2]
1.946
[3]
0.040
[14] array · 4 items
[0]
hsa03030
[1]
DNA replication
[2]
2.242
[3]
0.041
[15] array · 4 items
[0]
hsa03050
[1]
Proteasome
[2]
1.987
[3]
0.047
[16] array · 5 items
[0]
KEGG negative
[1]
hsa04725
[2]
Cholinergic synapse
[3]
−1.421
[4]
0.008
[17] array · 4 items
[0]
hsa04060
[1]
Cytokine-cytokine receptor interaction
[2]
−1.294
[3]
0.008
[18] array · 4 items
[0]
hsa04024
[1]
cAMP signaling pathway
[2]
−1.347
[3]
0.008
[19] array · 4 items
[0]
hsa04020
[1]
Calcium signaling pathway
[2]
−1.387
[3]
0.008
[20] array · 4 items
[0]
hsa04080
[1]
Neuroactive ligand-receptor interaction
[2]
−1.497
[3]
0.008
locator
section[11]/table-wrap[1]#t1-medscimonit-26-e925016
gaps array · 4 items
[0]
asset:data:geo:GSE32323 not downloaded
[1]
asset:data:geo:GSE32323 licence not read
[2]
asset:data:geo:GSE41258 not downloaded
[3]
asset:data:geo:GSE41258 licence not read
analysis object · 4 fields
state
partial
methods array · 4 items
[0] object · 10 fields
id
method-1
family
group_comparison
specific
mann_whitney
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_mann_whitney
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
1
band
verbatim
quote
The Mann-Whitney U test was performed to determine whether TIICs belong to different groups.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
band
medium
quote
COX regression
[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
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
0.7
band
medium
quote
Pearson correlation
targets array · 0 items
gaps array · 1 item
[0]
method.group_comparison_mann_whitney
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
false
required_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_mann_whitney
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: mann_whitney.
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 · 2 items
[0]
GSE41258
[1]
GSE32323
resolved_accessions array · 2 items
[0]
GSE41258
[1]
GSE32323
statements array · 1 item
[0]
Sequencing data on colon adenocarcinomas and corresponding clinical information in the TCGA were downloaded from the UCSC Xena database (https://xenabrowser.net/datapages/) [21], with org.Hs.eg.db (R package) used to annotate Ensembl ID.
basis
The paper names GSE41258, GSE32323 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 0 items
assets array · 3 items
[0]
source:pmid:32949121
[1]
data:geo:GSE32323
[2]
asset:table:pmid:32949121:1
steps array · 0 items
must_build object · 5 fields
dsl_operations array · 1 item
[0] object · 3 fields
operation
group_comparison_mann_whitney
priority
null
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE32323
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
2026-10-31T18:22:31Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
null
calls
3
usage object · 3 fields
prompt_tokens
31446
completion_tokens
1390
cached_tokens
792
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]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:32949121
type
paper
label
pmid:32949121
[1] object · 3 fields
id
source:pmid:32949121
type
manuscript
label
PMID 32949121 full text
[2] object · 3 fields
id
data:geo:GSE32323
type
dataset
label
GEO GSE32323
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:32949121
type
paper
label
pmid:32949121
[1] object · 3 fields
id
source:pmid:32949121
type
manuscript
label
PMID 32949121 full text
[2] object · 3 fields
id
data:geo:GSE32323
type
dataset
label
GEO GSE32323
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-32949121
type
extraction
used array · 1 item
[0]
source:pmid:32949121
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE32323
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE32323
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
label
MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:32949121
parent_hash
sha256:c198b1f2bede85171c092a35f76915abc9ac447a715cbc652773e593a0722b32
fork_of
null
gaps array · 10 items
[0]
asset:data:geo:GSE32323 licence not read
[1]
asset:data:geo:GSE32323 not downloaded
[2]
asset:data:geo:GSE41258 licence not read
[3]
asset:data:geo:GSE41258 not downloaded
[4]
execution.not_run
[5]
method.group_comparison_mann_whitney
[6]
review.human_critique
[7]
review.independent_reader
[8]
review.machine_critique
[9]
step:run_analysis blocked on method:group_comparison_mann_whitney
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
group_comparison
definition_version
f2132e96ae6c7a4e
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The Mann-Whitney U test was performed to determine whether TIICs belong to different groups.
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32949121", "kind": "science-record", "revision": 8, "content_hash": "sha256:8dfdf9d480283e951da63e1c88fb163ce7d6efb9825bf6da2fffa467342b46c7", "created_at": "2026-11-01T15:41:10Z", "updated_at": "2026-11-01T22:02:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic Value of SLC4A4 and its Correlation with Immune Infiltration in Colon Adenocarcinoma.", "doi": "10.12659/MSM.925016", "pmid": "32949121", "authors": ["Xiaoli Chen", "Jianing Chen", "Yan Feng", "Wei Guan"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2020, "abstract": "BACKGROUND SLC4A4 is differentially expressed in a variety of tumors, but its significance in colon adenocarcinoma has not been determined. MATERIAL AND METHODS Transcriptomes of two cohorts, GSE41258 and GSE32323, contained in The Cancer Genome Atlas (TCGA) were analysed to determine differences in SLC4A4 expression between tumor and normal tissue and their correlations with overall survival. The relationships between SLC4A4 expression and clinical characteristics were determined by COX regression analysis and logistic regression analysis, and correlations of SLC4A4 levels with tumor infiltrating immune cells (TIICs) and genes with high mutation frequency were evaluated by Pearson correlation analysis. Molecular functions and signaling pathways that might be affected by changes in SLC4A4 expression were determined by gene set enrichment analysis (GSEA). The overall distribution of TIICs was determined by two web servers: tumor immune estimation resource (TIMER) and CIBERSORT. RESULTS SLC4A4 expression was lower in colon adenocarcinoma than in normal colon tissue, suggesting that SLC4A4 was associated with poor prognosis. Reduced SLC4A4 expression was also associated with lymph node invasion and distant metastasis and was moderately correlated with increased expression of MUC4 and SMAD4, two genes with high mutation frequency in colon adenocarcinoma. GSEA indicated that changes in SLC4A4 expression affects several biological processes, including mismatch repair, base excision repair, and DNA replication. Eight TIICs in the tumor microenvironment differed significantly in groups with low and high expression of SLC4A4. CONCLUSIONS SLC4A4 may be a novel biomarker predicting prognosis in patients with colon adenocarcinoma. TIICs differed significantly in samples with higher and lower expression of SLC4A4.", "claims": [{"id": "claim-method", "statement": "The Mann-Whitney U test was performed to determine whether TIICs belong to different groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32949121", "locator": "sections[4] \"Immune infiltrates analysis\" paragraph 2", "quote": "The Mann-Whitney U test was performed to determine whether TIICs belong to different groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Sequencing data on colon adenocarcinomas and corresponding clinical information in the TCGA were downloaded from the UCSC Xena database (https://xenabrowser.net/datapages/) [21], with org.Hs.eg.db (R package) used to annotate Ensembl ID.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32949121", "locator": "sections[3] \"Clinical information and expression profile\" paragraph 2", "quote": "Sequencing data on colon adenocarcinomas and corresponding clinical information in the TCGA were downloaded from the UCSC Xena database (https://xenabrowser.net/datapages/) [21], with org.Hs.eg.db (R package) used to annotate Ensembl ID."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:32949121"], "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:GSE32323"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_mann_whitney", "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:GSE32323"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32949121", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12659/MSM.925016", "sha256": "sha256:8e091c43197c0daea2c591a6f5853b269faffea46a23f97eba43fda2c636ea72", "bytes": 41009, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.12659/MSM.925016", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7526338", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE32323", "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=GSE32323", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE32323", "version": null, "note": "Sequencing data on colon adenocarcinomas and corresponding clinical information in the TCGA were downloaded from the UCSC Xena database (https://xenabrowser.net/datapages/) [21], with org.Hs.eg.db (R package) used to annotate Ensembl ID.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Sequencing data on colon adenocarcinomas and corresponding clinical information in the TCGA were downloaded from the UCSC Xena database (https://xenabrowser.net/datapages/) [21], with org.Hs.eg.db (R package) used to annotate Ensembl ID.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM800742", "GSM800743", "GSM800744", "GSM800745", "GSM800746", "GSM800747", "GSM800748", "GSM800749", "GSM800750", "GSM800751", "GSM800752", "GSM800753", "GSM800754", "GSM800755", "GSM800756", "GSM800757", "GSM800758", "GSM800759", "GSM800760", "GSM800761", "GSM800762", "GSM800763", "GSM800764", "GSM800765", "GSM800766", "GSM800767", "GSM800768", "GSM800769", "GSM800770", "GSM800771", "GSM800772", "GSM800773", "GSM800774", "GSM800775", "GSM800776", "GSM800777", "GSM800778", "GSM800779", "GSM800780", "GSM800781", "GSM800782", "GSM800783", "GSM800784", "GSM800785"], "sample_count": 44, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Screening for Epigenetically Masked Genes in Colorectal Cancer using 5-aza-2’-deoxycytidine treatment, Microarray and Gene Expression Profile", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE41258", "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=GSE41258", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE41258", "version": null, "note": "Sequencing data on colon adenocarcinomas and 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