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pmid:36969015

A novel risk score model based on gamma-aminobutyric acid signature predicts the survival prognosis of patients with breast cancer.

Liping Yang · Jin Zhu · Lieliang Wang · Longbo He · Yi Gong · Qingfeng Luo

Frontiers in oncology · 2023 doi:10.3389/fonc.2023.1108823

Paper

complete

Experiment

complete

Data

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Analysis

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Execution

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pmid:36969015
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title
A novel risk score model based on gamma-aminobutyric acid signature predicts the survival prognosis of patients with breast cancer.
doi
10.3389/fonc.2023.1108823
pmid
36969015
authors array · 6 items
[0]
Liping Yang
[1]
Jin Zhu
[2]
Lieliang Wang
[3]
Longbo He
[4]
Yi Gong
[5]
Qingfeng Luo
journal
Frontiers in oncology
year
2023
abstract
Background: Gamma-aminobutyric acid (GABA) participates in the migration, differentiation, and proliferation of tumor cells. However, the GABA-related risk signature has never been investigated. Hence, we aimed to develop a reliable gene signature based on GABA pathways-related genes (GRGs) to predict the survival prognosis of breast cancer patients. Methods: GABA-related gene sets were acquired from the MSigDB database, while mRNA gene expression profiles and corresponding clinical data of breast cancer patients were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate Cox regression analysis was used to identify prognostic-associated GRGs. Subsequently, LASSO analysis was applied to establish a risk score model. We also constructed a clinical nomogram to perform the survival evaluation. Besides, ESTIMATE and ssGSEA algorithms were used to assess the immune cell infiltration among the risk score subgroups. Results: A GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort. The risk score was significantly related to the overall survival of breast cancer patients, which could predict the survival prognosis of breast cancer patients independently of other clinical features. Breast cancer patients in the low-risk score group exhibited higher immune cell infiltration levels. Conclusion: A novel prognostic model containing five GRGs could accurately predict the survival prognosis and immune infiltration of breast cancer patients. Our findings provided a novel insight into investigating the immunoregulation roles of GRGs.
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Subsequently, we used the “survival” and “glmnet” packages of R to carry out the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.
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sections[6] "Establishment of the prognostic risk score model based on DEGRGs" paragraph 2
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Subsequently, we used the “survival” and “glmnet” packages of R to carry out the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .
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A GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort.
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A GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort.
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A GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort.
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A gene expression signature identifies two prognostic subgroups of basal breast cancer
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[1]
asset:data:geo:GSE21653 licence not read
[2]
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[3]
asset:data:geo:GSE22820 licence not read
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state
complete
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family
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specific
cox_proportional_hazards
label
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dsl_operations array · 1 item
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cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
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time_to_event_with_censoring
evidence object · 3 fields
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quote
Subsequently, we used the “survival” and “glmnet” packages of R to carry out the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.
[1] object · 10 fields
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method-2
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network_analysis
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build_graph
[1]
centrality_scores
[2]
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evidence object · 3 fields
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0.8
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quote
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capability object · 3 fields
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candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
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tier
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method object · 5 fields
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cox_ph
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: cox_proportional_hazards.
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
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accessions array · 2 items
[0]
GSE21653
[1]
GSE22820
resolved_accessions array · 2 items
[0]
GSE21653
[1]
GSE22820
statements array · 1 item
[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .
basis
The paper names GSE21653, GSE22820 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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dsl_operations array · 1 item
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cox_ph
assets array · 2 items
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data_gaps array · 1 item
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data:geo:GSE21653
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review object · 5 fields
state
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machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T18:34:42Z
independence
single_reader
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method
verbatim
availability
verbatim
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5
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prompt_tokens
11402
completion_tokens
2273
cached_tokens
256
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[0] object · 4 fields
id
extraction
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MiniMax-M3.1-Flash
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review.human_critique
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absent
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not_run
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gaps array · 1 item
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execution.not_run
provenance object · 7 fields
entities array · 3 items
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pmid:36969015
type
paper
label
pmid:36969015
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id
source:pmid:36969015
type
manuscript
label
PMID 36969015 full text
[2] object · 3 fields
id
data:geo:GSE21653
type
dataset
label
GEO GSE21653
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[0] object · 4 fields
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activity-reading-sci-2026-11-01
type
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used array · 3 items
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pmid:36969015
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paper
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pmid:36969015
[1] object · 3 fields
id
source:pmid:36969015
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manuscript
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PMID 36969015 full text
[2] object · 3 fields
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data:geo:GSE21653
type
dataset
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GEO GSE21653
agent
agent:corpus-assay-engine
[1] object · 4 fields
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extraction
used array · 1 item
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agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE21653
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used array · 1 item
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agent:corpus-assay-engine
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[0] object · 3 fields
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agent:minimax-reader
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dsl_catalogue_fingerprint
343fb30756ba6ec3
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lineage object · 4 fields
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[3]
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[0] object · 11 fields
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99e1195c7d6f
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evidence array · 1 item
[0]
on. The qRT-PCR was carried out on a StepOne Real-time PCR system (Applied Biosystems). The 2–ΔΔCt meth
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paper_text_order:2852
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dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
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Subsequently, we used the “survival” and “glmnet” packages of R to carry out the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36969015", "kind": "science-record", "revision": 3, "content_hash": "sha256:c0570b260a0f56e6fdfbe31c7db548857747c0ada32b32fd3f6d91049235ed87", "created_at": "2026-11-01T19:01:36Z", "updated_at": "2026-11-01T22:09:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A novel risk score model based on gamma-aminobutyric acid signature predicts the survival prognosis of patients with breast cancer.", "doi": "10.3389/fonc.2023.1108823", "pmid": "36969015", "authors": ["Liping Yang", "Jin Zhu", "Lieliang Wang", "Longbo He", "Yi Gong", "Qingfeng Luo"], "journal": "Frontiers in oncology", "year": 2023, "abstract": "Background: Gamma-aminobutyric acid (GABA) participates in the migration, differentiation, and proliferation of tumor cells. However, the GABA-related risk signature has never been investigated. Hence, we aimed to develop a reliable gene signature based on GABA pathways-related genes (GRGs) to predict the survival prognosis of breast cancer patients.\nMethods: GABA-related gene sets were acquired from the MSigDB database, while mRNA gene expression profiles and corresponding clinical data of breast cancer patients were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate Cox regression analysis was used to identify prognostic-associated GRGs. Subsequently, LASSO analysis was applied to establish a risk score model. We also constructed a clinical nomogram to perform the survival evaluation. Besides, ESTIMATE and ssGSEA algorithms were used to assess the immune cell infiltration among the risk score subgroups.\nResults: A GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort. The risk score was significantly related to the overall survival of breast cancer patients, which could predict the survival prognosis of breast cancer patients independently of other clinical features. Breast cancer patients in the low-risk score group exhibited higher immune cell infiltration levels.\nConclusion: A novel prognostic model containing five GRGs could accurately predict the survival prognosis and immune infiltration of breast cancer patients. Our findings provided a novel insight into investigating the immunoregulation roles of GRGs.", "claims": [{"id": "claim-method", "statement": "Subsequently, we used the “survival” and “glmnet” packages of R to carry out the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36969015", "locator": "sections[6] \"Establishment of the prognostic risk score model based on DEGRGs\" paragraph 2", "quote": "Subsequently, we used the “survival” and “glmnet” packages of R to carry out the least absolute shrinkage and selection operator (LASSO) Cox regression analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36969015", "locator": "sections[21] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36969015", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort.", "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:36969015"], "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:GSE21653"], "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:GSE21653"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36969015", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2023.1108823", "sha256": "sha256:88a33c45d7abf7e60ab0b4e26b0605e93ef99f0daab45bc827e0b3071f22ba7d", "bytes": 36536, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2023.1108823", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10031029", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE21653", "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=GSE21653", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE21653", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM540108", "GSM540109", "GSM540110", "GSM540111", "GSM540112", "GSM540113", "GSM540114", "GSM540115", "GSM540116", "GSM540117", "GSM540118", "GSM540119", "GSM540120", "GSM540121", "GSM540122", "GSM540123", "GSM540124", "GSM540125", "GSM540126", "GSM540127", "GSM540128", "GSM540129", "GSM540130", "GSM540131", "GSM540132", "GSM540133", "GSM540134", "GSM540135", "GSM540136", "GSM540137", "GSM540138", "GSM540139", "GSM540140", "GSM540141", "GSM540142", "GSM540143", "GSM540144", "GSM540145", "GSM540146", "GSM540147", "GSM540148", "GSM540149", "GSM540150", "GSM540151", "GSM540152", "GSM540153", "GSM540154", "GSM540155", "GSM540156", "GSM540157", "GSM540158", "GSM540159", "GSM540160", "GSM540161", "GSM540162", "GSM540163", "GSM540164", "GSM540165", "GSM540166", "GSM540167", "GSM540168", "GSM540169", "GSM540170", "GSM540171", "GSM540172", "GSM540173", "GSM540174", "GSM540175", "GSM540176", "GSM540177", "GSM540178", "GSM540179", "GSM540180", "GSM540181", "GSM540182", "GSM540183", "GSM540184", "GSM540185", "GSM540186", "GSM540187", "GSM540188", "GSM540189", "GSM540190", "GSM540191", "GSM540192", "GSM540193", "GSM540194", "GSM540195", "GSM540196", "GSM540197", "GSM540198", "GSM540199", "GSM540200", "GSM540201", "GSM540202", "GSM540203", "GSM540204", "GSM540205", "GSM540206", "GSM540207", "GSM540208", "GSM540209", "GSM540210", "GSM540211", "GSM540212", "GSM540213", "GSM540214", "GSM540215", "GSM540216", "GSM540217", "GSM540218", "GSM540219", "GSM540220", "GSM540221", "GSM540222", "GSM540223", "GSM540224", "GSM540225", "GSM540226", "GSM540227", "GSM540228", "GSM540229", "GSM540230", "GSM540231", "GSM540232", "GSM540233", "GSM540234", "GSM540235", "GSM540236", "GSM540237", "GSM540238", "GSM540239", "GSM540240", "GSM540241", "GSM540242", "GSM540243", "GSM540244", "GSM540245", "GSM540246", "GSM540247", "GSM540248", "GSM540249", "GSM540250", "GSM540251", "GSM540252", "GSM540253", "GSM540254", "GSM540255", "GSM540256", "GSM540257", "GSM540258", "GSM540259", "GSM540260", "GSM540261", "GSM540262", "GSM540263", "GSM540264", "GSM540265", "GSM540266", "GSM540267", "GSM540268", "GSM540269", "GSM540270", "GSM540271", "GSM540272", "GSM540273", "GSM540274", "GSM540275", "GSM540276", "GSM540277", "GSM540278", "GSM540279", "GSM540280", "GSM540281", "GSM540282", "GSM540283", "GSM540284", "GSM540285", "GSM540286", "GSM540287", "GSM540288", "GSM540289", "GSM540290", "GSM540291", "GSM540292", "GSM540293", "GSM540294", "GSM540295", "GSM540296", "GSM540297", "GSM540298", "GSM540299", "GSM540300", "GSM540301", "GSM540302", "GSM540303", "GSM540304", "GSM540305", "GSM540306", "GSM540307", "GSM540308", "GSM540309", "GSM540310", "GSM540311", "GSM540312", "GSM540313", "GSM540314", "GSM540315", "GSM540316", "GSM540317", "GSM540318", "GSM540319", "GSM540320", "GSM540321", "GSM540322", "GSM540323", "GSM540324", "GSM540325", "GSM540326", "GSM540327", "GSM540328", "GSM540329", "GSM540330", "GSM540331", "GSM540332", "GSM540333", "GSM540334", "GSM540335", "GSM540336", "GSM540337", "GSM540338", "GSM540339", "GSM540340", "GSM540341", "GSM540342", "GSM540343", "GSM540344", "GSM540345", "GSM540346", "GSM540347", "GSM540348", "GSM540349", "GSM540350", "GSM540351", "GSM540352", "GSM540353", "GSM540354", "GSM540355", "GSM540356", "GSM540357", "GSM540358", "GSM540359", "GSM540360", "GSM540361", "GSM540362", "GSM540363", "GSM540364", "GSM540365", "GSM540366", "GSM540367", "GSM540368", "GSM540369", "GSM540370", "GSM540371", "GSM540372", "GSM540373"], "sample_count": 266, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "A gene expression signature identifies two prognostic subgroups of basal breast cancer", "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:GSE22820", "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=GSE22820", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE22820", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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"high", "quote": "PPI"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"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": {"tier": "R1", "reachable": true, "accessions": ["GSE21653", "GSE22820"], "resolved_accessions": ["GSE21653", "GSE22820"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."], "basis": "The paper names GSE21653, GSE22820 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:36969015", "data:geo:GSE21653"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE21653"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:34:42Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11402, "completion_tokens": 2273, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36969015", "type": "paper", "label": "pmid:36969015"}, {"id": "source:pmid:36969015", "type": "manuscript", "label": "PMID 36969015 full text"}, {"id": "data:geo:GSE21653", "type": "dataset", "label": "GEO GSE21653"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36969015", "type": "paper", "label": "pmid:36969015"}, {"id": "source:pmid:36969015", "type": "manuscript", "label": "PMID 36969015 full text"}, {"id": "data:geo:GSE21653", "type": "dataset", "label": "GEO GSE21653"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36969015", "type": "extraction", "used": ["source:pmid:36969015"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE21653", "type": "accession_resolution", "used": ["data:geo:GSE21653"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"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": {"parent_id": "pmid:36969015", "parent_hash": "sha256:788f9e078254f865cbeb1b83a9b70982f63deafe778b96b17103b54fcfb43c75", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE21653 licence not read", "asset:data:geo:GSE21653 not downloaded", "asset:data:geo:GSE22820 licence not read", "asset:data:geo:GSE22820 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["on. 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