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pmid:39071697

Single cell transcriptomic analysis reveals tumor immune infiltration by NK cells gene signature in lung adenocarcinoma.

Yimin Zhu · Xiuhua Wu · Yunjiao Zhang · Jie Gu · Rongwei Zhou · Zhong Guo

Heliyon · 2024 doi:10.1016/j.heliyon.2024.e33928

Paper

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Single cell transcriptomic analysis reveals tumor immune infiltration by NK cells gene signature in lung adenocarcinoma.
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10.1016/j.heliyon.2024.e33928
pmid
39071697
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Yimin Zhu
[1]
Xiuhua Wu
[2]
Yunjiao Zhang
[3]
Jie Gu
[4]
Rongwei Zhou
[5]
Zhong Guo
journal
Heliyon
year
2024
abstract
Background: Natural Killer (NK) cells are vital components of the innate immune system, crucial for combating infections and tumor growth, making them pivotal in cancer prognosis and immunotherapy. We sought to understand the diverse characteristics of NK cells within lung adenocarcinoma (LUAD) by conducting single-cell RNA sequencing analyses. Methods: Using the scRNA-seq dataset for multiple primary lung cancers (MPLCs), we examined two major NK cell groups, NK1 and NK2, comparing the expression profiles of 422 differentially expressed NK signature genes. We identified eight genes (SPON2, PLEKHG3, CAMK2N1, RAB27B, CTBP2, EFHD2, GOLM1, and PLOD1) that distinguish NK1 from NK2 cells. A prognostic signature, the NK gene signature (NKGS) score, was established through LASSO Cox regression. High NKGS scores were linked to poorer overall survival in TCGA-LUAD patients and consistently validated in other datasets (GSE31210 and GSE14814). Results: Functional analysis revealed an enrichment of genes related to the TGF-β signaling pathway in the high NKGS score group. Moreover, a high NKGS score correlated with an immunosuppressive tumor microenvironment (TME) driven by immune evasion mechanisms. We also observed reduced T-cell receptor (TCR) repertoire diversity in the high-risk NKGS group, indicating a negative association between inflammation and risk score. Conclusion: This study introduced the innovative NKGS score, differentiating NK1 from NK2 cells. High NKGS scores were associated with the TGF-β pathway and provided insights into LUAD prognosis and immune activities.
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These genes were then evaluated using the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression via the “glmnet” R package.
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These genes were then evaluated using the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression via the “glmnet” R package.
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The single-cell RNA-seq dataset was sourced from the GEO database using the accession number GSE200972. We obtained the TCGA-LUAD cohort dataset from The Cancer Genome Atlas (TCGA) portal (https://portal.gdc.cancer.gov/). Additionally, we retrieved datasets GSE31210 and GSE14814 from the GEO database.
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The single-cell RNA-seq dataset was sourced from the GEO database using the accession number GSE200972. We obtained the TCGA-LUAD cohort dataset from The Cancer Genome Atlas (TCGA) portal (https://portal.gdc.cancer.gov/). Additionally, we retrieved datasets GSE31210 and GSE14814 from the GEO database.
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The high NKGS risk group exhibited significantly poorer overall survival than the low-risk group in TCGA-LUAD (HR = 1.76, P = 0.00016).
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Kaplan–Meier (KM) analysis illustrated that high-risk patients exhibited markedly diminished overall survival (OS) compared to their low-risk counterparts (Fig. 4A, HR = 1.76, P = 0.00016).
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sections[5] "Construction of the prognostic signature based on NK cell signature genes" paragraph 3
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Kaplan–Meier (KM) analysis illustrated that high-risk patients exhibited markedly diminished overall survival (OS) compared to their low-risk counterparts (Fig. 4A, HR = 1.76, P = 0.00016).
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The high NKGS risk group exhibited significantly poorer overall survival than the low-risk group in TCGA-LUAD (HR = 1.76, P = 0.00016).
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[245]
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sample_count
246
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene expression data for pathological stage I-II lung adenocarcinomas
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
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licence_read
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gaps array · 6 items
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asset:data:geo:GSE14814 not downloaded
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[3]
asset:data:geo:GSE200972 licence not read
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asset:data:geo:GSE31210 licence not read
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state
complete
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specific
cox_proportional_hazards
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Survival analysis
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cox_ph
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data_shapes array · 1 item
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time_to_event_with_censoring
evidence object · 3 fields
score
1
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verbatim
quote
These genes were then evaluated using the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression via the “glmnet” R package.
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target-published-estimate
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claim-target-result
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hazard ratio
tolerance
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state
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note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
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unit
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state
complete
note
The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold.
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capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
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assay_families array · 9 items
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[8]
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
axes object · 3 fields
method object · 5 fields
tier
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required_operations array · 1 item
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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 · 3 items
[0]
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GSE31210
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resolved_accessions array · 3 items
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statements array · 1 item
[0]
The single-cell RNA-seq dataset was sourced from the GEO database using the accession number GSE200972. We obtained the TCGA-LUAD cohort dataset from The Cancer Genome Atlas (TCGA) portal (https://portal.gdc.cancer.gov/). Additionally, we retrieved datasets GSE31210 and GSE14814 from the GEO database.
basis
The paper names GSE200972, GSE31210, GSE14814 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 · 1 item
[0]
cox_ph
assets array · 2 items
[0]
source:pmid:39071697
[1]
data:geo:GSE14814
steps array · 1 item
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run_analysis
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data_gaps array · 1 item
[0]
data:geo:GSE14814
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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
2026-11-01T19:25:57Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
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5
usage object · 3 fields
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10515
completion_tokens
2232
cached_tokens
128
stages array · 1 item
[0] object · 4 fields
id
extraction
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complete
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minimax
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gaps array · 1 item
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provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:39071697
type
paper
label
pmid:39071697
[1] object · 3 fields
id
source:pmid:39071697
type
manuscript
label
PMID 39071697 full text
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id
data:geo:GSE14814
type
dataset
label
GEO GSE14814
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
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id
pmid:39071697
type
paper
label
pmid:39071697
[1] object · 3 fields
id
source:pmid:39071697
type
manuscript
label
PMID 39071697 full text
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id
data:geo:GSE14814
type
dataset
label
GEO GSE14814
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-39071697
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extraction
used array · 1 item
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source:pmid:39071697
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE14814
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accession_resolution
used array · 1 item
[0]
data:geo:GSE14814
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agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
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Corpus assay engine
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id
agent:minimax-reader
type
software
label
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dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
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lineage object · 4 fields
parent_id
pmid:39071697
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sha256:7eb1f2886e0c73321c3dbbc0d1f67dc39ab1ecd0b4d31f445553978ac362b149
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[1]
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assays array · 3 items
[0] object · 11 fields
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data_generation
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partial
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assay_lexicon
99e1195c7d6f
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evidence array · 2 items
[0]
Single cell transcriptomic analysis reveals tumor immune infiltration b
[1]
nocarcinoma (LUAD) by conducting single-cell RNA sequencing analyses. Methods: Using the scRNA-seq datas
order_basis
paper_text_order:0
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assay:1
[1] object · 11 fields
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[0]
hin lung adenocarcinoma (LUAD) by conducting single-cell RNA sequencing analyses. Methods: Using the scRNA-seq datas
[1]
RNA sequencing analyses. Methods: Using the scRNA-seq dataset for multiple primary lung cancers (M
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paper_text_order:386
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f2132e96ae6c7a4e
evidence array · 1 item
[0]
These genes were then evaluated using the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression via the “glmnet” R package.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39071697", "kind": "science-record", "revision": 2, "content_hash": "sha256:fe811fe6ec7475864e3c38db04767ca18318b249891d654b3c18802d01c4dba9", "created_at": "2026-11-01T20:29:08Z", "updated_at": "2026-11-01T21:33:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Single cell transcriptomic analysis reveals tumor immune infiltration by NK cells gene signature in lung adenocarcinoma.", "doi": "10.1016/j.heliyon.2024.e33928", "pmid": "39071697", "authors": ["Yimin Zhu", "Xiuhua Wu", "Yunjiao Zhang", "Jie Gu", "Rongwei Zhou", "Zhong Guo"], "journal": "Heliyon", "year": 2024, "abstract": "Background: Natural Killer (NK) cells are vital components of the innate immune system, crucial for combating infections and tumor growth, making them pivotal in cancer prognosis and immunotherapy. We sought to understand the diverse characteristics of NK cells within lung adenocarcinoma (LUAD) by conducting single-cell RNA sequencing analyses.\nMethods: Using the scRNA-seq dataset for multiple primary lung cancers (MPLCs), we examined two major NK cell groups, NK1 and NK2, comparing the expression profiles of 422 differentially expressed NK signature genes. We identified eight genes (SPON2, PLEKHG3, CAMK2N1, RAB27B, CTBP2, EFHD2, GOLM1, and PLOD1) that distinguish NK1 from NK2 cells. A prognostic signature, the NK gene signature (NKGS) score, was established through LASSO Cox regression. High NKGS scores were linked to poorer overall survival in TCGA-LUAD patients and consistently validated in other datasets (GSE31210 and GSE14814).\nResults: Functional analysis revealed an enrichment of genes related to the TGF-β signaling pathway in the high NKGS score group. Moreover, a high NKGS score correlated with an immunosuppressive tumor microenvironment (TME) driven by immune evasion mechanisms. We also observed reduced T-cell receptor (TCR) repertoire diversity in the high-risk NKGS group, indicating a negative association between inflammation and risk score.\nConclusion: This study introduced the innovative NKGS score, differentiating NK1 from NK2 cells. High NKGS scores were associated with the TGF-β pathway and provided insights into LUAD prognosis and immune activities.", "claims": [{"id": "claim-method", "statement": "These genes were then evaluated using the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression via the “glmnet” R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39071697", "locator": "sections[14] \"Construction and validation of the prognostic signature\" paragraph 2", "quote": "These genes were then evaluated using the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression via the “glmnet” R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The single-cell RNA-seq dataset was sourced from the GEO database using the accession number GSE200972. We obtained the TCGA-LUAD cohort dataset from The Cancer Genome Atlas (TCGA) portal (https://portal.gdc.cancer.gov/). 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE14814"], "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:GSE14814"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39071697", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2024.e33928", "sha256": "sha256:98247047073af1f4e2246ba94b4a26a21ee4e3276d11dc4710efb2a3c4779590", "bytes": 38040, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2024.e33928", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11283104", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14814", "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=GSE14814", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14814", "version": null, "note": "The single-cell RNA-seq dataset was sourced from the GEO database using the accession number GSE200972. 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