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pmid:37539127

Analysis and application of RNA binding protein gene pairs to predict the prognosis of gastric cancer.

Zhi-Kun Ning · Hua-Kai Tian · Jiang Liu · Ce-Gui Hu · Zi-Tao Liu · Hui Li · Zhen Zong

Heliyon · 2023 doi:10.1016/j.heliyon.2023.e18242

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title
Analysis and application of RNA binding protein gene pairs to predict the prognosis of gastric cancer.
doi
10.1016/j.heliyon.2023.e18242
pmid
37539127
authors array · 7 items
[0]
Zhi-Kun Ning
[1]
Hua-Kai Tian
[2]
Jiang Liu
[3]
Ce-Gui Hu
[4]
Zi-Tao Liu
[5]
Hui Li
[6]
Zhen Zong
journal
Heliyon
year
2023
abstract
Background: RNA-binding proteins (RBPs) are closely related to tumors, but little is known about the mechanism of RBPs in tumorigenesis and progression of gastric cancer (GC). As genes do not usually act alone in the pathway deregulation, gene pair combinations are more likely to become stable and accurate biomarkers. The purpose of our research is to establish a novel signature based on RBP gene pairs to predict the prognosis of gastric cancer patients. Methods: We downloaded genetic and clinical information from the TCGA and GEO database. TCGA and GSE13911 were used for screening differentially expressed genes (DEGs). The RBP genes were gathered from previous studies and employed to screen out DE-RBP genes after intersecting with DEGs. Samples were classified according to the relative expression of each pair of DE-RBP genes. The univariate Cox regression analysis and random forest were used to identify hub gene pairs to construct signature for predicting the prognosis of gastric cancer. Time-dependent ROC curves and KM survival curves were performed to evaluate the signature. GSEA was performed in TCGA training cohort and GSE62254 testing cohort to analyze enrichment pathways. Finally, the influence of these gene pairs on the prognosis of GC patients was further elucidated respectively through the combination of high and low expression of the two genes in each hub gene pair. Results: We screened out 6 hub RBP gene pairs (COL5A2/FEN1, POP1/GFRA1, EXO1/PLEKHS1, SLC39A10/CHI3L1, MMP7/PPP1R1 B and SLC5A6/BYSL) to predict the prognosis of patients with gastric cancer. Using the optimal cut-off value to divide patients into high-risk and low-risk groups in the training and testing cohort, we found that the overall survival (OS) of the low-risk group was higher than that of the high-risk group (P < 0.05). The area under the ROC curves for 1, 3, and 5 years were (0.659, 0.744, 0.758) and (0.624, 0.650, 0.653) in two cohorts. Univariate and multivariate Cox regression analysis showed that 6 RBP gene pairs signature were independent prognostic factors for gastric cancer (P < 0.05). In addition, the prognostic survival analysis showed that COL5A2-high/FEN1-low, POP1-low/GFRA1-high, EXO1-low/PLEKHS1-low,SLC39A10-high/CHI3L1-low, MMP7-high/PPP1R1 B-low, SLC5A6-low/BYSL-low had worse OS (P < 0.05). And the gene correlation analysis showed that there was no obvious correlation between the genes in each gene pairs except SLC5A6/BYSL and POP1/GFRA1. Finally, GSEA analysis showed that the high-risk group was enriched in tumor migration, invasion and growth-related pathways. Conclusion: Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy.
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We performed univariate and multivariate Cox proportional-hazards analysis to identify independent prognostic factors using the “rms” R package in TCGA and GSE62254.
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We performed univariate and multivariate Cox proportional-hazards analysis to identify independent prognostic factors using the “rms” R package in TCGA and GSE62254.
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Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy.
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Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy.
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differential_expression_fit
[2]
fdr_bh
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parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
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0.8
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high
quote
DESeq2
[4] object · 10 fields
id
method-5
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differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
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[1]
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[2]
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parameters object · 0 fields
data_shapes array · 1 item
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count_matrix_with_condition
evidence object · 3 fields
score
0.8
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high
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limma
[5] object · 10 fields
id
method-6
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machine_learning
specific
random_forest
label
Machine learning
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missing_operations array · 1 item
[0]
machine_learning_random_forest
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
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quote
random forest
[6] object · 10 fields
id
method-7
family
correlation_analysis
specific
pearson
label
Correlation analysis
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[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
0.8
band
high
quote
Pearson correlation
[7] object · 10 fields
id
method-8
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
0.8
band
high
quote
pathway enrichment
[8] object · 10 fields
id
method-9
family
null
specific
null
label
Univariate and multivariate Cox proportional-hazards analysis
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
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quote
We performed univariate and multivariate Cox proportional-hazards analysis to identify independent prognostic factors using the “rms” R package in TCGA and GSE62254.
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gaps array · 1 item
[0]
method.reader_named_unmapped
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
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readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
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true
required_operations array · 1 item
[0]
survival_km
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: kaplan_meier.
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
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[0]
GSE13911
[1]
GSE62254
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[0]
GSE13911
[1]
GSE62254
statements array · 1 item
[0]
The authors are unable or have chosen not to specify which data has been used.
basis
The paper names GSE13911, 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 · 1 item
[0]
survival_km
assets array · 2 items
[0]
source:pmid:37539127
[1]
data:geo:GSE13911
steps array · 1 item
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run_analysis
must_build object · 5 fields
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readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE13911
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
2026-11-01T18:48:54Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
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5
usage object · 3 fields
prompt_tokens
10304
completion_tokens
1855
cached_tokens
264
stages array · 1 item
[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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[1]
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[2]
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absent
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not_run
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null
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provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:37539127
type
paper
label
pmid:37539127
[1] object · 3 fields
id
source:pmid:37539127
type
manuscript
label
PMID 37539127 full text
[2] object · 3 fields
id
data:geo:GSE13911
type
dataset
label
GEO GSE13911
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
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[0] object · 3 fields
id
pmid:37539127
type
paper
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pmid:37539127
[1] object · 3 fields
id
source:pmid:37539127
type
manuscript
label
PMID 37539127 full text
[2] object · 3 fields
id
data:geo:GSE13911
type
dataset
label
GEO GSE13911
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-37539127
type
extraction
used array · 1 item
[0]
source:pmid:37539127
agent
agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE13911
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accession_resolution
used array · 1 item
[0]
data:geo:GSE13911
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
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software
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Corpus assay engine
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id
agent:minimax-reader
type
software
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MiniMax literature reader
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dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:37539127
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sha256:ae124666c7705a002a92180c471676dbecfff26b0cd9371e198a053459cad764
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null
gaps array · 9 items
[0]
asset:data:geo:GSE13911 licence not read
[1]
asset:data:geo:GSE13911 not downloaded
[2]
asset:data:geo:GSE62254 licence not read
[3]
asset:data:geo:GSE62254 not downloaded
[4]
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[5]
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[6]
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[7]
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[8]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
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f2132e96ae6c7a4e
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survival_km
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supported
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dsl_catalogue
f2132e96ae6c7a4e
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37539127", "kind": "science-record", "revision": 3, "content_hash": "sha256:7e866d97e4d9f1cb2997e78d3cf5a46e9d78bb4314c01739f967995db2a4fece", "created_at": "2026-11-01T19:02:19Z", "updated_at": "2026-11-01T22:10:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis and application of RNA binding protein gene pairs to predict the prognosis of gastric cancer.", "doi": "10.1016/j.heliyon.2023.e18242", "pmid": "37539127", "authors": ["Zhi-Kun Ning", "Hua-Kai Tian", "Jiang Liu", "Ce-Gui Hu", "Zi-Tao Liu", "Hui Li", "Zhen Zong"], "journal": "Heliyon", "year": 2023, "abstract": "Background: RNA-binding proteins (RBPs) are closely related to tumors, but little is known about the mechanism of RBPs in tumorigenesis and progression of gastric cancer (GC). As genes do not usually act alone in the pathway deregulation, gene pair combinations are more likely to become stable and accurate biomarkers. The purpose of our research is to establish a novel signature based on RBP gene pairs to predict the prognosis of gastric cancer patients.\nMethods: We downloaded genetic and clinical information from the TCGA and GEO database. TCGA and GSE13911 were used for screening differentially expressed genes (DEGs). The RBP genes were gathered from previous studies and employed to screen out DE-RBP genes after intersecting with DEGs. Samples were classified according to the relative expression of each pair of DE-RBP genes. The univariate Cox regression analysis and random forest were used to identify hub gene pairs to construct signature for predicting the prognosis of gastric cancer. Time-dependent ROC curves and KM survival curves were performed to evaluate the signature. GSEA was performed in TCGA training cohort and GSE62254 testing cohort to analyze enrichment pathways. Finally, the influence of these gene pairs on the prognosis of GC patients was further elucidated respectively through the combination of high and low expression of the two genes in each hub gene pair.\nResults: We screened out 6 hub RBP gene pairs (COL5A2/FEN1, POP1/GFRA1, EXO1/PLEKHS1, SLC39A10/CHI3L1, MMP7/PPP1R1 B and SLC5A6/BYSL) to predict the prognosis of patients with gastric cancer. Using the optimal cut-off value to divide patients into high-risk and low-risk groups in the training and testing cohort, we found that the overall survival (OS) of the low-risk group was higher than that of the high-risk group (P < 0.05). The area under the ROC curves for 1, 3, and 5 years were (0.659, 0.744, 0.758) and (0.624, 0.650, 0.653) in two cohorts. Univariate and multivariate Cox regression analysis showed that 6 RBP gene pairs signature were independent prognostic factors for gastric cancer (P < 0.05). In addition, the prognostic survival analysis showed that COL5A2-high/FEN1-low, POP1-low/GFRA1-high, EXO1-low/PLEKHS1-low,SLC39A10-high/CHI3L1-low, MMP7-high/PPP1R1 B-low, SLC5A6-low/BYSL-low had worse OS (P < 0.05). And the gene correlation analysis showed that there was no obvious correlation between the genes in each gene pairs except SLC5A6/BYSL and POP1/GFRA1. Finally, GSEA analysis showed that the high-risk group was enriched in tumor migration, invasion and growth-related pathways.\nConclusion: Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy.", "claims": [{"id": "claim-method", "statement": "We performed univariate and multivariate Cox proportional-hazards analysis to identify independent prognostic factors using the “rms” R package in TCGA and GSE62254.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37539127", "locator": "sections[8] \"Independent prognostic factors\" paragraph 2", "quote": "We performed univariate and multivariate Cox proportional-hazards analysis to identify independent prognostic factors using the “rms” R package in TCGA and GSE62254."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors are unable or have chosen not to specify which data has been used.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37539127", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "The authors are unable or have chosen not to specify which data has been used."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37539127", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy.", "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:37539127"], "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:GSE13911"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE13911"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37539127", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2023.e18242", "sha256": 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