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pmid:41266429

Constructing a sixteen lactate-related gene risk signature for LUAD to predict the prognosis and TME by machine learning.

Jinjie Wang · Deshen Shan · Hailong Tang · Ming Zhao · Hao Wang

Scientific reports · 2025 doi:10.1038/s41598-025-24770-6

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Constructing a sixteen lactate-related gene risk signature for LUAD to predict the prognosis and TME by machine learning.
doi
10.1038/s41598-025-24770-6
pmid
41266429
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Jinjie Wang
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Deshen Shan
[2]
Hailong Tang
[3]
Ming Zhao
[4]
Hao Wang
journal
Scientific reports
year
2025
abstract
Although it is the most common subtype of lung cancer in clinical practice, lung adenocarcinoma (LUAD) was proven to be associated with a poor prognosis. In recent years, lactate metabolism has been considered an important biological mechanism in lung cancer. However, the mechanisms of lactate-related genes in tumour microenvironment (TME) of LUAD are unknown. Lactate-related genes modification patterns in 701 LUAD samples from TCGA and GEO database were systematically assessed on the basis of 16 lactate-related genes (LRGs).We also identified the correlation of these clusters to the TME and immune cell infiltration in the TME. After unsupervised clustering analysis was performed, the LUAD samples were divided into three lactate-related gene phenotypes on the basis of 36 prognostic lactate-related genes (PLRGs). These molecular subtypes have different immune cell infiltration characteristics and pathway enrichment. Using LASSO, a 16-LRG risk signature was constructed. The lactate-related signature demonstrated a stable and accurate ability to predict the prognosis of LUAD in patients. Furthermore, the lactate-related signature demonstrated good predictive ability for immune infiltrating cells, tumour mutation burden, and response to immunotherapy. The 16-LRG risk signature was subsequently verified in the GSE50081 GEO cohort. This study revealed the significant clinical utility of the 16-LRG risk signature in the understanding the TME and prognosis of LUAD. The 16-LRG risk signature is conducive to understanding immune cell infiltration in the LUAD TME and contributes to the selection of more effective immunotherapy strategies.
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LASSO was used to construct a sixteen-gene prognostic signature based on the screened LRGs.
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sections[8] "Construction and validation of the lactate-related signature" paragraph 2
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LASSO was used to construct a sixteen-gene prognostic signature based on the screened LRGs.
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The datasets generated during and/or analysed during the current study are available from GEO [https://www.ncbi.nlm.nih.gov/geo/] (https://www.ncbi.nlm.nih.gov/geo) and TCGA official website (https://portal.gdc.cancer.gov/repository).
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The 16-LRG risk signature achieved an AUC of 0.692 for prognostic prediction.
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sections[14] "Assessment of the correlation between the prognostic signature and clinical features" paragraph 2
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The AUC of the 16-LRG risk signature was 0.692 (Fig. 4A).
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The 16-LRG risk signature achieved an AUC of 0.692 for prognostic prediction.
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GSM1019333
sample_count
196
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null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis and tissue microarray validation
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
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false
licence_read
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[3] object · 15 fields
id
data:geo:GSE50081
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raw
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geo-series
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application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50081
sha256
null
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null
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null
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null
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The datasets generated during and/or analysed during the current study are available from GEO [https://www.ncbi.nlm.nih.gov/geo/] (https://www.ncbi.nlm.nih.gov/geo) and TCGA official website (https://portal.gdc.cancer.gov/repository).
structure object · 15 fields
repository
GEO
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GEO accession URL
access_statement_verbatim
The datasets generated during and/or analysed during the current study are available from GEO [https://www.ncbi.nlm.nih.gov/geo/] (https://www.ncbi.nlm.nih.gov/geo) and TCGA official website (https://portal.gdc.cancer.gov/repository).
access_statement_kind
data_availability_statement
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181
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Validation of a histology-independent prognostic gene signature for early stage, non-small cell lung cancer including stage IA patients
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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gaps array · 6 items
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[4]
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[5]
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analysis object · 4 fields
state
partial
methods array · 2 items
[0] object · 10 fields
id
method-1
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survival_analysis
specific
cox_proportional_hazards
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cox_ph
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time_to_event_with_censoring
evidence object · 3 fields
score
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LASSO was used to construct a sixteen-gene prognostic signature based on the screened LRGs.
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id
method-2
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network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
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[0]
pathway_enrich
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edge_list
evidence object · 3 fields
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medium
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pathway enrichment
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method.reader_differs_from_extractor
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
label
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assay_families array · 9 items
[0]
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gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
complete
tier
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blocked_on
nothing:replicable_now
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cox_ph
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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
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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 · 3 items
[0]
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GSE50081
resolved_accessions array · 3 items
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GSE30219
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GSE50081
statements array · 1 item
[0]
The datasets generated during and/or analysed during the current study are available from GEO [https://www.ncbi.nlm.nih.gov/geo/] (https://www.ncbi.nlm.nih.gov/geo) and TCGA official website (https://portal.gdc.cancer.gov/repository).
basis
The paper names GSE30219, GSE37745, GSE50081 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
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cox_ph
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source:pmid:41266429
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data:geo:GSE30219
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run_analysis
must_build object · 5 fields
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[0]
data:geo:GSE30219
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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
2026-11-01T20:06:08Z
independence
single_reader
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method
verbatim
availability
verbatim
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5
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id
extraction
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complete
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minimax
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review.human_critique
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not_run
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paper
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pmid:41266429
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source:pmid:41266429
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manuscript
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PMID 41266429 full text
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data:geo:GSE30219
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dataset
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GEO GSE30219
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[0] object · 4 fields
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activity-reading-sci-2026-11-01
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classification
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paper
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source:pmid:41266429
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PMID 41266429 full text
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dataset
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GEO GSE30219
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agent:corpus-assay-engine
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activity-read-41266429
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extraction
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agent:minimax-reader
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activity-resolve-GSE30219
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agent:corpus-assay-engine
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LASSO was used to construct a sixteen-gene prognostic signature based on the screened LRGs.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41266429", "kind": "science-record", "revision": 2, "content_hash": "sha256:0936da854143b91db8c65c24f5adf4886e12d72722f04f4017e64cc7089cf743", "created_at": "2026-11-01T20:31:17Z", "updated_at": "2026-11-01T21:36:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Constructing a sixteen lactate-related gene risk signature for LUAD to predict the prognosis and TME by machine learning.", "doi": "10.1038/s41598-025-24770-6", "pmid": "41266429", "authors": ["Jinjie Wang", "Deshen Shan", "Hailong Tang", "Ming Zhao", "Hao Wang"], "journal": "Scientific reports", "year": 2025, "abstract": "Although it is the most common subtype of lung cancer in clinical practice, lung adenocarcinoma (LUAD) was proven to be associated with a poor prognosis. In recent years, lactate metabolism has been considered an important biological mechanism in lung cancer. However, the mechanisms of lactate-related genes in tumour microenvironment (TME) of LUAD are unknown. Lactate-related genes modification patterns in 701 LUAD samples from TCGA and GEO database were systematically assessed on the basis of 16 lactate-related genes (LRGs).We also identified the correlation of these clusters to the TME and immune cell infiltration in the TME. After unsupervised clustering analysis was performed, the LUAD samples were divided into three lactate-related gene phenotypes on the basis of 36 prognostic lactate-related genes (PLRGs). These molecular subtypes have different immune cell infiltration characteristics and pathway enrichment. Using LASSO, a 16-LRG risk signature was constructed. The lactate-related signature demonstrated a stable and accurate ability to predict the prognosis of LUAD in patients. Furthermore, the lactate-related signature demonstrated good predictive ability for immune infiltrating cells, tumour mutation burden, and response to immunotherapy. The 16-LRG risk signature was subsequently verified in the GSE50081 GEO cohort. This study revealed the significant clinical utility of the 16-LRG risk signature in the understanding the TME and prognosis of LUAD. The 16-LRG risk signature is conducive to understanding immune cell infiltration in the LUAD TME and contributes to the selection of more effective immunotherapy strategies.", "claims": [{"id": "claim-method", "statement": "LASSO was used to construct a sixteen-gene prognostic signature based on the screened LRGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41266429", "locator": "sections[8] \"Construction and validation of the lactate-related signature\" paragraph 2", "quote": "LASSO was used to construct a sixteen-gene prognostic signature based on the screened LRGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analysed during the current study are available from GEO [https://www.ncbi.nlm.nih.gov/geo/] (https://www.ncbi.nlm.nih.gov/geo) and TCGA official website (https://portal.gdc.cancer.gov/repository).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41266429", "locator": "sections[26] \"notes\" paragraph 1", "quote": "The datasets generated during and/or analysed during the current study are available from GEO [https://www.ncbi.nlm.nih.gov/geo/] (https://www.ncbi.nlm.nih.gov/geo) and TCGA official website (https://portal.gdc.cancer.gov/repository)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The 16-LRG risk signature achieved an AUC of 0.692 for prognostic prediction.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41266429", "locator": "sections[14] \"Assessment of the correlation between the prognostic signature and clinical features\" paragraph 2", "quote": "The AUC of the 16-LRG risk signature was 0.692 (Fig. 4A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The 16-LRG risk signature achieved an AUC of 0.692 for prognostic prediction.", "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:41266429"], "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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