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pmid:33217815

Aberrant brain-expressed X-linked 4 (BEX4) expression is a novel prognostic biomarker in gastric cancer.

Chenhong Zhu · Deshuang Xiao

Medicine · 2020 doi:10.1097/MD.0000000000023133

Paper

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Experiment

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Data

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Aberrant brain-expressed X-linked 4 (BEX4) expression is a novel prognostic biomarker in gastric cancer.
doi
10.1097/MD.0000000000023133
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33217815
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Chenhong Zhu
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Deshuang Xiao
journal
Medicine
year
2020
abstract
BACKGROUND: This study aimed to investigate the expression level of X-linked 4 (BEX4) in patients with gastric cancer (GC) and to investigate the prognostic significance of BEX4. METHODS: The mRNA expression of BEX4 was analyzed using the Cancer Genome Atlas (TCGA) datasets. The relationship between the expression of BEX4 and GC patient survival was assessed using a Kaplan-Meier plot and Log Rank test. Multivariate cox regression analysis was used to evaluate prognostic factor. The diagnostic value of BEX4 expression in GC tissue was determined through receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was used to explore BEX-4 related signaling pathways in GC. Furthermore, the Human Protein Atlas (HPA) database and GSE62254 dataset were used for further validation. RESULTS: BEX4 was expressed at lower level in GC tissues than normal gastric tissues. The lower expression of BEX4 was also validated at protein level in HPA database. The area under the ROC curve for BEX4 expression in normal gastric tissue and GC was 0.791, which presented modest diagnostic value. Kaplan-Meier survival analysis revealed that patients in low BEX4 expression group had a worse prognosis than those with high BEX4 expression (P = .009). Multivariate analysis showed that BEX4 is an independent risk factor for overall survival both in TCGA and GSE62254 (P = .0142, .013, respectively). GSEA identified that the expression of BEX4 was related to DNA replication, RNA polymerase, cell cycle, and P53 signaling pathway. CONCLUSION: BEX4 is expressed at low levels in GC. BEX4 expression independently predicted poor OS for GC. It is a promising independent molecular predictor for the diagnosis and prognosis of GC.
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Expression levels of BEX4 in 375 GC and 32 normal gastric tissues were compared using Wilcoxon signed-rank test, and the results revealed that BEX4 was lower expressed in GC compared to normal tissues (P < .001) (Figure. 2A).
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sections[8] "Association of BEX4 expression with clinical variables" paragraph 2
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Expression levels of BEX4 in 375 GC and 32 normal gastric tissues were compared using Wilcoxon signed-rank test, and the results revealed that BEX4 was lower expressed in GC compared to normal tissues (P < .001) (Figure. 2A).
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Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study [gastric tumors]
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Association of BEX4 expression with clinical variables
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Univariate and multivariate analysis of the relationship of BEX4 expression with overall survival among gastric cancer patients.
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Diagnostic and prognostic value of BEX4 expression in GC
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Univariate and multivariate analysis of the relationship of BEX4 expression with overall survival among gastric cancer patients.
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[3] array · 7 items
[0]
Cancer subtype
[1]
1.128
[2]
0.857-1.483
[3]
.391
[4]
1.004
[5]
0.741-1.359
[6]
.979
[4] array · 7 items
[0]
Helicobacter pylori infection
[1]
0.605
[2]
0.253-1.448
[3]
.259
[4]
0.536
[5]
0.210-1.365
[6]
.191
[5] array · 7 items
[0]
Age
[1]
1.039
[2]
1.009-1.071
[3]
.01
[4]
1.049
[5]
1.017-1.083
[6]
.003
[6] array · 7 items
[0]
Gender
[1]
1.634
[2]
0.892-2.995
[3]
.112
[4]
1.589
[5]
0.836-3.019
[6]
.157
[7] array · 7 items
[0]
Grade
[1]
1.352
[2]
0.840-2.177
[3]
.213
[4]
1.502
[5]
0.884-2.549
[6]
.133
[8] array · 7 items
[0]
Stage
[1]
1.672
[2]
1.157-2.417
[3]
.006
[4]
1.865
[5]
1.251-2.779
[6]
.002
[9] array · 7 items
[0]
BEX4 expression
[1]
0.632
[2]
0.420-0.844
[3]
.0215
[4]
0.627
[5]
0.431-0.823
[6]
.0201
locator
section[9]/table-wrap[1]#T2
gaps array · 2 items
[0]
asset:data:geo:GSE62254 not downloaded
[1]
asset:data:geo:GSE62254 licence not read
analysis object · 4 fields
state
partial
methods array · 6 items
[0] object · 10 fields
id
method-1
family
group_comparison
specific
wilcoxon
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
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
Expression levels of BEX4 in 375 GC and 32 normal gastric tissues were compared using Wilcoxon signed-rank test, and the results revealed that BEX4 was lower expressed in GC compared to normal tissues (P < .001) (Figure. 2A).
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
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
Kaplan-Meier
[2] object · 10 fields
id
method-3
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
[3] object · 10 fields
id
method-4
family
survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[0]
logrank_test
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
Log Rank
[4] object · 10 fields
id
method-5
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
0.8
band
high
quote
logistic regression
[5] object · 10 fields
id
method-6
family
diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
[1]
roc_curve
[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.7
band
medium
quote
ROC curve
targets array · 0 items
gaps array · 1 item
[0]
method.group_comparison_wilcoxon
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_wilcoxon
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon.
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]
GSE62254
resolved_accessions array · 1 item
[0]
GSE62254
statements array · 1 item
[0]
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
basis
The paper names GSE62254 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 · 0 items
assets array · 4 items
[0]
source:pmid:33217815
[1]
data:geo:GSE62254
[2]
asset:table:pmid:33217815:1
[3]
asset:table:pmid:33217815:2
steps array · 0 items
must_build object · 5 fields
dsl_operations array · 1 item
[0] object · 3 fields
operation
group_comparison_wilcoxon
priority
null
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE62254
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
2026-10-31T18:24:21Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
16528
completion_tokens
1683
cached_tokens
784
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:33217815
type
paper
label
pmid:33217815
[1] object · 3 fields
id
source:pmid:33217815
type
manuscript
label
PMID 33217815 full text
[2] object · 3 fields
id
data:geo:GSE62254
type
dataset
label
GEO GSE62254
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:33217815
type
paper
label
pmid:33217815
[1] object · 3 fields
id
source:pmid:33217815
type
manuscript
label
PMID 33217815 full text
[2] object · 3 fields
id
data:geo:GSE62254
type
dataset
label
GEO GSE62254
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-33217815
type
extraction
used array · 1 item
[0]
source:pmid:33217815
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE62254
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE62254
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:33217815
parent_hash
sha256:fa495c26c78e7f5df67bd7657d33823b3814aa1747226f5e321a59845636e68f
fork_of
null
gaps array · 8 items
[0]
asset:data:geo:GSE62254 licence not read
[1]
asset:data:geo:GSE62254 not downloaded
[2]
execution.not_run
[3]
method.group_comparison_wilcoxon
[4]
review.human_critique
[5]
review.independent_reader
[6]
review.machine_critique
[7]
step:run_analysis blocked on method:group_comparison_wilcoxon
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]
Expression levels of BEX4 in 375 GC and 32 normal gastric tissues were compared using Wilcoxon signed-rank test, and the results revealed that BEX4 was lower expressed in GC compared to normal tissues (P < .001) (Figure. 2A).
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:33217815", "kind": "science-record", "revision": 7, "content_hash": "sha256:e0974a5457ff40f51946e58bf4d066e638332652f8684bbd014a150992d26c51", "created_at": "2026-11-01T15:41:16Z", "updated_at": "2026-11-01T22:02:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Aberrant brain-expressed X-linked 4 (BEX4) expression is a novel prognostic biomarker in gastric cancer.", "doi": "10.1097/MD.0000000000023133", "pmid": "33217815", "authors": ["Chenhong Zhu", "Deshuang Xiao"], "journal": "Medicine", "year": 2020, "abstract": "BACKGROUND: This study aimed to investigate the expression level of X-linked 4 (BEX4) in patients with gastric cancer (GC) and to investigate the prognostic significance of BEX4.\nMETHODS: The mRNA expression of BEX4 was analyzed using the Cancer Genome Atlas (TCGA) datasets. The relationship between the expression of BEX4 and GC patient survival was assessed using a Kaplan-Meier plot and Log Rank test. Multivariate cox regression analysis was used to evaluate prognostic factor. The diagnostic value of BEX4 expression in GC tissue was determined through receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was used to explore BEX-4 related signaling pathways in GC. Furthermore, the Human Protein Atlas (HPA) database and GSE62254 dataset were used for further validation.\nRESULTS: BEX4 was expressed at lower level in GC tissues than normal gastric tissues. The lower expression of BEX4 was also validated at protein level in HPA database. The area under the ROC curve for BEX4 expression in normal gastric tissue and GC was 0.791, which presented modest diagnostic value. Kaplan-Meier survival analysis revealed that patients in low BEX4 expression group had a worse prognosis than those with high BEX4 expression (P = .009). Multivariate analysis showed that BEX4 is an independent risk factor for overall survival both in TCGA and GSE62254 (P = .0142, .013, respectively). GSEA identified that the expression of BEX4 was related to DNA replication, RNA polymerase, cell cycle, and P53 signaling pathway.\nCONCLUSION: BEX4 is expressed at low levels in GC. BEX4 expression independently predicted poor OS for GC. It is a promising independent molecular predictor for the diagnosis and prognosis of GC.", "claims": [{"id": "claim-method", "statement": "Expression levels of BEX4 in 375 GC and 32 normal gastric tissues were compared using Wilcoxon signed-rank test, and the results revealed that BEX4 was lower expressed in GC compared to normal tissues (P < .001) (Figure. 2A).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33217815", "locator": "sections[8] \"Association of BEX4 expression with clinical variables\" paragraph 2", "quote": "Expression levels of BEX4 in 375 GC and 32 normal gastric tissues were compared using Wilcoxon signed-rank test, and the results revealed that BEX4 was lower expressed in GC compared to normal tissues (P < .001) (Figure. 2A)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33217815", "locator": "sections[15] \"fn-group\" paragraph 1", "quote": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "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:33217815"], "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:GSE62254"], "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_wilcoxon", "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:GSE62254"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33217815", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1097/MD.0000000000023133", "sha256": "sha256:676a42ce89e6d512583d7b82d80c78b7e63a35a06db70beda21174b7cc81d8df", "bytes": 21350, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1097/MD.0000000000023133", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7676604", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE62254", "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=GSE62254", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE62254", "version": null, "note": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1523727", "GSM1523728", "GSM1523729", "GSM1523744", "GSM1523745", "GSM1523746", "GSM1523747", "GSM1523748", "GSM1523765", "GSM1523768", "GSM1523769", "GSM1523770", "GSM1523771", "GSM1523772", "GSM1523773", "GSM1523774", "GSM1523775", "GSM1523776", "GSM1523777", "GSM1523778", "GSM1523779", "GSM1523780", "GSM1523781", "GSM1523782", "GSM1523783", "GSM1523784", "GSM1523785", "GSM1523786", "GSM1523787", "GSM1523788", "GSM1523789", "GSM1523790", "GSM1523791", "GSM1523792", "GSM1523793", "GSM1523794", "GSM1523795", "GSM1523796", "GSM1523797", "GSM1523798", "GSM1523799", "GSM1523800", 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survival among gastric cancer patients.", "structure": {"pmcid": "PMC7676604", "section_index": 9, "section_title": "Diagnostic and prognostic value of BEX4 expression in GC", "row_count": 10, "column_count": 7}, "table": {"label": "Table 2", "caption": "Univariate and multivariate analysis of the relationship of BEX4 expression with overall survival among gastric cancer patients.", "rows": [["", "Univariate analysis", "Multivariate analysis"], ["Variables", "HR", "95%CI", "P value", "HR", "95%CI", "P value"], ["Cancer regions", "1.055", "0.851-1.307", ".623", "1.055", "0.837-1.329", ".648"], ["Cancer subtype", "1.128", "0.857-1.483", ".391", "1.004", "0.741-1.359", ".979"], ["Helicobacter pylori infection", "0.605", "0.253-1.448", ".259", "0.536", "0.210-1.365", ".191"], ["Age", "1.039", "1.009-1.071", ".01", "1.049", "1.017-1.083", ".003"], ["Gender", "1.634", "0.892-2.995", ".112", "1.589", "0.836-3.019", ".157"], ["Grade", "1.352", "0.840-2.177", ".213", "1.502", "0.884-2.549", 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