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pmid:34863300

Prognostic value of immune-related genes and comparative analysis of immune cell infiltration in lung adenocarcinoma: sex differences.

Tao Fan · Chunxiang Li · Jie He

Biology of sex differences · 2021 doi:10.1186/s13293-021-00406-y

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Experiment

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Data

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pmid:34863300
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2026-11-01T17:36:34Z
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2026-11-01T22:05:17Z
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title
Prognostic value of immune-related genes and comparative analysis of immune cell infiltration in lung adenocarcinoma: sex differences.
doi
10.1186/s13293-021-00406-y
pmid
34863300
authors array · 3 items
[0]
Tao Fan
[1]
Chunxiang Li
[2]
Jie He
journal
Biology of sex differences
year
2021
abstract
BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most important subtypes of lung cancer. Compared with male LUAD patients, female patients have a higher incidence, but better long-term survival rate, with unknown reasons. In this study, we aimed to explore the effect of sex differences on immune cell infiltration in lung tumor microenvironment (TME), and tried to clarify the reasons for the different clinical characteristics of male and female LUAD patients, by conducting a comparative analysis of the TME. METHODS: Using ESTIMATE algorithm, we calculated immune and stromal scores of tumor samples downloaded from TCGA database according to immune or stromal components in TME. GO and KEGG enrichment analysis were conducted to reveal biological processes of these intersecting genes of high- and low-score groups. Cox regression analysis and protein-protein interaction (PPI) network analysis were performed to screen immune-related prognostic genes in female (CCR2, LCP2, and PTPRC) and male (BTK and CCR2) patients. Kaplan-Meier survival analysis was used to evaluate prognostic value of these identified genes. Mann-Whitney test was used to compare various indicators of male patients and female patients. The main results were subsequently validated in 420 cases from GSE72094. RESULTS: 304 and 368 intersecting genes were identified in female and male patients, respectively. The immune score ranged from -943.17 to 3229.35 among female patients and from -541.75 to 3441.78 among male patients. The stromal score ranged from -1790.23 to 2097.27 among female patients and from -1786.94 to 1722.70 among male patients. The immune and stromal scores of women were higher than those of men (p < 0.05). CCR2, LCP2 and PTPRC were identified as the most important immune-related prognostic genes in female LUAD patients. BTK and CCR2 were identified as the most important immune-related prognostic genes in male LUAD patients. Female patients had a higher proportion of memory B cells than that of male patients, while the percentage of T cells CD4 naïve and resting NK cells was lower in female patients (p < 0.05). CONCLUSIONS: This study comprehensively compared the differences in tumor immune microenvironment between male and female LUAD patients, and identified prognosis-related genes for patients of different sexes.
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The estimate, immune, and stromal scores of female LUAD patients were compared with that of male LUAD patients using GraphPad Prism 8.
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sections[9] "Statistical analysis" paragraph 2
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The estimate, immune, and stromal scores of female LUAD patients were compared with that of male LUAD patients using GraphPad Prism 8.
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The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.
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The immune and stromal scores of women were higher than those of men (p < 0.05).
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The immune and stromal scores of women were higher than those of men (p < 0.05).
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The immune and stromal scores of women were higher than those of men (p < 0.05).
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The immune and stromal scores of women were higher than those of men (p < 0.05).
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evidence object · 3 fields
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quote
Mann-Whitney
[1] object · 10 fields
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group_comparison
specific
wilcoxon
label
Group comparison
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missing_operations array · 1 item
[0]
group_comparison_wilcoxon
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parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
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high
quote
Wilcoxon
[2] object · 10 fields
id
method-3
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survival_analysis
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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
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0.7
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[3] object · 10 fields
id
method-4
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survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
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[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
[4] object · 10 fields
id
method-5
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network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
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data_shapes array · 1 item
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evidence object · 3 fields
score
0.7
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quote
protein-protein interaction
[5] object · 10 fields
id
method-6
family
null
specific
null
label
Mann–Whitney U test
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missing_operations array · 0 items
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data_shapes array · 0 items
evidence object · 3 fields
score
1
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verbatim
quote
The estimate, immune, and stromal scores of female LUAD patients were compared with that of male LUAD patients using GraphPad Prism 8.
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[0] object · 8 fields
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target-published-estimate
claim_id
claim-target-result
operation
build_graph
unit
p-value
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null
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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.
gaps array · 2 items
[0]
method.reader_named_unmapped
[1]
method.group_comparison_mann_whitney
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
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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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state
complete
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method object · 5 fields
tier
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missing_operations array · 1 item
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group_comparison_mann_whitney
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: mann_whitney.
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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true
accessions array · 1 item
[0]
GSE72094
resolved_accessions array · 1 item
[0]
GSE72094
statements array · 1 item
[0]
The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.
basis
The paper names GSE72094 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
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assets array · 2 items
[0]
source:pmid:34863300
[1]
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steps array · 0 items
must_build object · 5 fields
dsl_operations array · 1 item
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group_comparison_mann_whitney
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null
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capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE72094
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
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MiniMax-M3.1-Flash
provider
minimax
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minimax
read_at
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independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
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5
usage object · 3 fields
prompt_tokens
11333
completion_tokens
1475
cached_tokens
128
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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minimax
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review.independent_reader
[1]
review.machine_critique
[2]
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execution object · 5 fields
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absent
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not_run
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null
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gaps array · 1 item
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provenance object · 7 fields
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[0] object · 3 fields
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pmid:34863300
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paper
label
pmid:34863300
[1] object · 3 fields
id
source:pmid:34863300
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manuscript
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PMID 34863300 full text
[2] object · 3 fields
id
data:geo:GSE72094
type
dataset
label
GEO GSE72094
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
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pmid:34863300
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paper
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pmid:34863300
[1] object · 3 fields
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source:pmid:34863300
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manuscript
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PMID 34863300 full text
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data:geo:GSE72094
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dataset
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GEO GSE72094
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
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extraction
used array · 1 item
[0]
source:pmid:34863300
agent
agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE72094
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accession_resolution
used array · 1 item
[0]
data:geo:GSE72094
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
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agent:corpus-assay-engine
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software
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Corpus assay engine
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agent:minimax-reader
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software
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MiniMax literature reader
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dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
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ba34b49490d9bfaf
lineage object · 4 fields
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pmid:34863300
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sha256:4e190cfbb0254a47b3e885e630564296fa2449ddf8b799c67eb8e5c8b3cd4991
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null
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asset:data:geo:GSE72094 licence not read
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step:run_analysis blocked on method:group_comparison_mann_whitney
assays array · 1 item
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role
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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:34863300", "kind": "science-record", "revision": 4, "content_hash": "sha256:a6e7c85817303112fed83134146c00a0c5bdaf0d95ceec1cef98b150d2de85c7", "created_at": "2026-11-01T17:36:34Z", "updated_at": "2026-11-01T22:05:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic value of immune-related genes and comparative analysis of immune cell infiltration in lung adenocarcinoma: sex differences.", "doi": "10.1186/s13293-021-00406-y", "pmid": "34863300", "authors": ["Tao Fan", "Chunxiang Li", "Jie He"], "journal": "Biology of sex differences", "year": 2021, "abstract": "BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most important subtypes of lung cancer. Compared with male LUAD patients, female patients have a higher incidence, but better long-term survival rate, with unknown reasons. In this study, we aimed to explore the effect of sex differences on immune cell infiltration in lung tumor microenvironment (TME), and tried to clarify the reasons for the different clinical characteristics of male and female LUAD patients, by conducting a comparative analysis of the TME.\nMETHODS: Using ESTIMATE algorithm, we calculated immune and stromal scores of tumor samples downloaded from TCGA database according to immune or stromal components in TME. GO and KEGG enrichment analysis were conducted to reveal biological processes of these intersecting genes of high- and low-score groups. Cox regression analysis and protein-protein interaction (PPI) network analysis were performed to screen immune-related prognostic genes in female (CCR2, LCP2, and PTPRC) and male (BTK and CCR2) patients. Kaplan-Meier survival analysis was used to evaluate prognostic value of these identified genes. Mann-Whitney test was used to compare various indicators of male patients and female patients. The main results were subsequently validated in 420 cases from GSE72094.\nRESULTS: 304 and 368 intersecting genes were identified in female and male patients, respectively. The immune score ranged from -943.17 to 3229.35 among female patients and from -541.75 to 3441.78 among male patients. The stromal score ranged from -1790.23 to 2097.27 among female patients and from -1786.94 to 1722.70 among male patients. The immune and stromal scores of women were higher than those of men (p < 0.05). CCR2, LCP2 and PTPRC were identified as the most important immune-related prognostic genes in female LUAD patients. BTK and CCR2 were identified as the most important immune-related prognostic genes in male LUAD patients. Female patients had a higher proportion of memory B cells than that of male patients, while the percentage of T cells CD4 naïve and resting NK cells was lower in female patients (p < 0.05).\nCONCLUSIONS: This study comprehensively compared the differences in tumor immune microenvironment between male and female LUAD patients, and identified prognosis-related genes for patients of different sexes.", "claims": [{"id": "claim-method", "statement": "The estimate, immune, and stromal scores of female LUAD patients were compared with that of male LUAD patients using GraphPad Prism 8.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34863300", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "The estimate, immune, and stromal scores of female LUAD patients were compared with that of male LUAD patients using GraphPad Prism 8."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34863300", "locator": "sections[29] \"notes\" paragraph 1", "quote": "The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The immune and stromal scores of women were higher than those of men (p < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "The immune and stromal scores of women were higher than those of men (p < 0.05)."}, "evidence": [{"asset": "source:pmid:34863300", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The immune and stromal scores of women were higher than those of men (p < 0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The immune and stromal scores of women were higher than those of men (p < 0.05).", "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:34863300"], "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:GSE72094"], "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_mann_whitney", "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:GSE72094"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34863300", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13293-021-00406-y", "sha256": "sha256:a6bc425870d392810982245495c942b1a6f4ec86fe43309e8ffd70405c24f903", "bytes": 39137, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13293-021-00406-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8642994", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE72094", "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=GSE72094", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE72094", "version": null, "note": "The data sets used and/or analysed 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 data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1854797", "GSM1854798", "GSM1854799", "GSM1854800", "GSM1854801", "GSM1854802", "GSM1854803", "GSM1854804", "GSM1854805", "GSM1854806", "GSM1854807", "GSM1854808", "GSM1854809", "GSM1854810", "GSM1854811", "GSM1854812", "GSM1854813", "GSM1854814", "GSM1854815", "GSM1854816", "GSM1854817", "GSM1854818", "GSM1854819", "GSM1854820", "GSM1854821", "GSM1854822", "GSM1854823", "GSM1854824", "GSM1854825", "GSM1854826", "GSM1854827", "GSM1854828", "GSM1854829", "GSM1854830", "GSM1854831", "GSM1854832", "GSM1854833", "GSM1854834", "GSM1854835", "GSM1854836", "GSM1854837", "GSM1854838", "GSM1854839", "GSM1854840", 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