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pmid:33314730

Immune landscape and a promising immune prognostic model associated with TP53 in early-stage lung adenocarcinoma.

Chengde Wu · Xiang Rao · Wei Lin

Cancer medicine · 2021 doi:10.1002/cam4.3655

Paper

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Experiment

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Data

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Analysis

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title
Immune landscape and a promising immune prognostic model associated with TP53 in early-stage lung adenocarcinoma.
doi
10.1002/cam4.3655
pmid
33314730
authors array · 3 items
[0]
Chengde Wu
[1]
Xiang Rao
[2]
Wei Lin
journal
Cancer medicine
year
2021
abstract
PURPOSE: TP53 mutation, one of the most frequent mutations in early-stage lung adenocarcinoma (LUAD), triggers a series of alterations in the immune landscape, progression, and clinical outcome of early-stage LUAD. Our study was designed to unravel the effects of TP53 mutation on the immunophenotype of early-stage LUAD and formulate a TP53-associated immune prognostic model (IPM) that can estimate prognosis in early-stage LUAD patients. MATERIALS AND METHODS: Immune-associated differentially expressed genes (DEGs) between TP53 mutated (TP53MUT ) and TP53 wild-type (TP53WT ) early-stage LUAD were comprehensively analyzed. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis identified the prognostic immune-associated DEGs. We constructed and validated an IPM based on the TCGA and a meta-GEO composed of GSE72094, GSE42127, and GSE31210, respectively. The CIBERSORT algorithm was analyzed for assessing the percentage of immune cell types. A nomogram model was established for clinical application. RESULTS: TP53 mutation occurred in approximately 50.00% of LUAD patients, stimulating a weakened immune response in early-stage LUAD. Sixty-seven immune-associated DEGs were determined between TP53WT and TP53MUT cohort. An IPM consisting of two prognostic immune-associated DEGs (risk score = 0.098 * ENTPD2 expression + 0.168 * MIF expression) was developed through 397 cases in the TCGA and further validated based on 623 patients in a meta-GEO. The IPM stratified patients into low or high risk of undesirable survival and was identified as an independent prognostic indicator in multivariate analysis (HR = 2.09, 95% CI: 1.43-3.06, p < 0.001). Increased expressions of PD-L1, CTLA-4, and TIGIT were revealed in the high-risk group. Prognostic nomogram incorporating the IPM and other clinicopathological parameters (TNM stage and age) achieved optimal predictive accuracy and clinical utility. CONCLUSION: The IPM based on TP53 status is a reliable and robust immune signature to identify early-stage LUAD patients with high risk of unfavorable survival.
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sample_count
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group_sizes
null
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null
platform
15048
taxon
Homo sapiens
title
KRAS mutation-associated gene expression, p53 and STK11 mutations, proliferation and immune surveillance in lung adenocarcinoma
resolution_checked_at
2026-11-01T15:39:55Z
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section[13]/table-wrap[1]#cam43655-tbl-0001
version
null
note
Univariate Cox analysis of immune‐associated DEGs between TP53WT and TP53MUT early‐stage LUAD
structure object · 5 fields
pmcid
PMC7897963
section_index
13
section_title
Establishment of an IPM based on the TCGA database
row_count
7
column_count
3
table object · 8 fields
label
Table 1
caption
Univariate Cox analysis of immune‐associated DEGs between TP53WT and TP53MUT early‐stage LUAD
rows array · 7 items
[0] array · 3 items
[0]
Gene
[1]
HR (95% CI)
[2]
p value
[1] array · 3 items
[0]
C8B
[1]
0.92 (0.86–0.98)
[2]
0.0105
[2] array · 3 items
[0]
C6
[1]
0.91 (0.85–0.98)
[2]
0.0138
[3] array · 3 items
[0]
PLA2G1B
[1]
0.92 (0.86–0.99)
[2]
0.019
[4] array · 3 items
[0]
ENTPD2
[1]
1.12 (1.02–1.24)
[2]
0.0243
[5] array · 3 items
[0]
MIF
[1]
1.21 (1.02–1.43)
[2]
0.0277
[6] array · 3 items
[0]
C8A
[1]
0.91 (0.84–0.99)
[2]
0.0358
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section[13]/table-wrap[1]#cam43655-tbl-0001
[5] object · 16 fields
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section[17]/table-wrap[1]#cam43655-tbl-0002
version
null
note
Correlation of immunotherapy‐related genes and IPM risk score in early‐stage LUAD patients
structure object · 5 fields
pmcid
PMC7897963
section_index
17
section_title
Immune landscapes between early‐stage LUAD patients with low and high risk score
row_count
10
column_count
4
table object · 8 fields
label
Table 2
caption
Correlation of immunotherapy‐related genes and IPM risk score in early‐stage LUAD patients
rows array · 10 items
[0] array · 4 items
[0]
Variable 1
[1]
Variable 2
[2]
Pearson correlation coefficient
[3]
p value
[1] array · 4 items
[0]
Risk score
[1]
CTLA4
[2]
0.1406689
[3]
0.004986
[2] array · 4 items
[0]
Risk score
[1]
PD‐L1
[2]
0.1628738
[3]
0.001127
[3] array · 4 items
[0]
Risk score
[1]
TIM−3
[2]
0.1874968
[3]
0.1511717
[4] array · 4 items
[0]
Risk score
[1]
LAG3
[2]
0.0623279
[3]
0.2153
[5] array · 4 items
[0]
Risk score
[1]
TIGIT
[2]
0.1085566
[3]
0.03058
[6] array · 4 items
[0]
Risk score
[1]
IDO1
[2]
−0.1572216
[3]
0.061676
[7] array · 4 items
[0]
Risk score
[1]
CD4
[2]
−0.2581735
[3]
1.823e‐07
[8] array · 4 items
[0]
Risk score
[1]
CD8A
[2]
−0.1381627
[3]
0.005826
[9] array · 4 items
[0]
Risk score
[1]
CD8B
[2]
−0.06999592
[3]
0.1639
locator
section[17]/table-wrap[1]#cam43655-tbl-0002
gaps array · 6 items
[0]
asset:data:geo:GSE31210 not downloaded
[1]
asset:data:geo:GSE31210 licence not read
[2]
asset:data:geo:GSE42127 not downloaded
[3]
asset:data:geo:GSE42127 licence not read
[4]
asset:data:geo:GSE72094 not downloaded
[5]
asset:data:geo:GSE72094 licence not read
analysis object · 4 fields
state
complete
methods array · 5 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
cox_proportional_hazards
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Survival analysis
dsl_operations array · 1 item
[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
1
band
reordered
quote
“LASSO Cox analysis was conducted to identify two immune‐associated DEGs (ENTPD2 and MIF) with the optimal prognostic efficiency in patients.”
[1] object · 10 fields
id
method-2
family
principal_component_analysis
specific
pca
label
Principal component analysis
dsl_operations array · 1 item
[0]
pca_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
wide_numeric_matrix
evidence object · 3 fields
score
0.8
band
high
quote
principal components analysis
[2] object · 10 fields
id
method-3
family
differential_expression
specific
edger
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Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
0.8
band
high
quote
edgeR
[3] object · 10 fields
id
method-4
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differential_expression
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limma_voom
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Differential expression analysis
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[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
0.8
band
high
quote
limma
[4] object · 10 fields
id
method-5
family
correlation_analysis
specific
pearson
label
Correlation analysis
dsl_operations array · 1 item
[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
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
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statistical_regression
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[5]
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gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
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complete
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nothing:replicable_now
axes object · 3 fields
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
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Publicly available datasets were analyzed in this study. These data can be found here: https://tcga‐data.nci.nih.gov/tcga/ and http://www.ncbi.nlm.nih.gov/geo/.
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cSniper Variant Aggregation and Masking) and RNA sequencing (RNA‐seq) data and the corresponding clinico
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on values of the same gene were detected. 35 Microarray data and the corresponding clinical informat
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“LASSO Cox analysis was conducted to identify two immune‐associated DEGs (ENTPD2 and MIF) with the optimal prognostic efficiency in patients.”
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33314730", "kind": "science-record", "revision": 7, "content_hash": "sha256:655b84ecde929560d5a02627e86e33fbf13970971cad4ee88eafd6d4dcddfcb4", "created_at": "2026-11-01T15:41:19Z", "updated_at": "2026-11-01T22:02:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Immune landscape and a promising immune prognostic model associated with TP53 in early-stage lung adenocarcinoma.", "doi": "10.1002/cam4.3655", "pmid": "33314730", "authors": ["Chengde Wu", "Xiang Rao", "Wei Lin"], "journal": "Cancer medicine", "year": 2021, "abstract": "PURPOSE: TP53 mutation, one of the most frequent mutations in early-stage lung adenocarcinoma (LUAD), triggers a series of alterations in the immune landscape, progression, and clinical outcome of early-stage LUAD. Our study was designed to unravel the effects of TP53 mutation on the immunophenotype of early-stage LUAD and formulate a TP53-associated immune prognostic model (IPM) that can estimate prognosis in early-stage LUAD patients.\nMATERIALS AND METHODS: Immune-associated differentially expressed genes (DEGs) between TP53 mutated (TP53MUT ) and TP53 wild-type (TP53WT ) early-stage LUAD were comprehensively analyzed. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis identified the prognostic immune-associated DEGs. We constructed and validated an IPM based on the TCGA and a meta-GEO composed of GSE72094, GSE42127, and GSE31210, respectively. The CIBERSORT algorithm was analyzed for assessing the percentage of immune cell types. A nomogram model was established for clinical application.\nRESULTS: TP53 mutation occurred in approximately 50.00% of LUAD patients, stimulating a weakened immune response in early-stage LUAD. Sixty-seven immune-associated DEGs were determined between TP53WT and TP53MUT cohort. An IPM consisting of two prognostic immune-associated DEGs (risk score = 0.098 * ENTPD2 expression + 0.168 * MIF expression) was developed through 397 cases in the TCGA and further validated based on 623 patients in a meta-GEO. The IPM stratified patients into low or high risk of undesirable survival and was identified as an independent prognostic indicator in multivariate analysis (HR = 2.09, 95% CI: 1.43-3.06, p < 0.001). Increased expressions of PD-L1, CTLA-4, and TIGIT were revealed in the high-risk group. Prognostic nomogram incorporating the IPM and other clinicopathological parameters (TNM stage and age) achieved optimal predictive accuracy and clinical utility.\nCONCLUSION: The IPM based on TP53 status is a reliable and robust immune signature to identify early-stage LUAD patients with high risk of unfavorable survival.", "claims": [{"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found here: https://tcga‐data.nci.nih.gov/tcga/ and http://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33314730", "locator": "sections[27] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE31210"], "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:GSE31210"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33314730", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/cam4.3655", "sha256": "sha256:ce73e58c8094d8642d57f6691da32959e917433b5440f138ec457798e20a3471", "bytes": 65804, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1002/cam4.3655", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7897963", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE31210", "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=GSE31210", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31210", "version": null, "note": "Publicly available datasets were analyzed in this study. 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