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pmid:34416861

Characteristic of molecular subtypes in lung adenocarcinoma based on m6A RNA methylation modification and immune microenvironment.

Hao Zhou · Miaosen Zheng · Muqi Shi · Jinjie Wang · Zhanghao Huang · Haijian Zhang · Youlang Zhou · Jiahai Shi

BMC cancer · 2021 doi:10.1186/s12885-021-08655-1

Paper

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Data

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title
Characteristic of molecular subtypes in lung adenocarcinoma based on m6A RNA methylation modification and immune microenvironment.
doi
10.1186/s12885-021-08655-1
pmid
34416861
authors array · 8 items
[0]
Hao Zhou
[1]
Miaosen Zheng
[2]
Muqi Shi
[3]
Jinjie Wang
[4]
Zhanghao Huang
[5]
Haijian Zhang
[6]
Youlang Zhou
[7]
Jiahai Shi
journal
BMC cancer
year
2021
abstract
BACKGROUND: Lung adenocarcinoma (LUAD) is a major subtype of lung cancer and closely associated with poor prognosis. N6-methyladenosine (m6A), one of the most predominant modifications in mRNAs, is found to participate in tumorigenesis. However, the potential function of m6A RNA methylation in the tumor immune microenvironment is still murky. METHODS: The gene expression profile cohort and its corresponding clinical data of LUAD patients were downloaded from TCGA database and GEO database. Based on the expression of 21 m6A regulators, we identified two distinct subgroups by consensus clustering. The single-sample gene-set enrichment analysis (ssGSEA) algorithm was conducted to quantify the relative abundance of the fraction of 28 immune cell types. The prognostic model was constructed by Lasso Cox regression. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate the prognostic model. RESULT: Consensus classification separated the patients into two clusters (clusters 1 and 2). Those patients in cluster 1 showed a better prognosis and were related to higher immune scores and more immune cell infiltration. Subsequently, 457 differentially expressed genes (DEGs) between the two clusters were identified, and then a seven-gene prognostic model was constricted. The survival analysis showed poor prognosis in patients with high-risk score. The ROC curve confirmed the predictive accuracy of this prognostic risk signature. Besides, further analysis indicated that there were significant differences between the high-risk and low-risk groups in stages, status, clustering subtypes, and immunoscore. Low-risk group was related to higher immune score, more immune cell infiltration, and lower clinical stages. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. Ultimately, the efficacy of this prognostic model was successfully validated in several external cohorts (GSE30219, GSE50081 and GSE72094). CONCLUSION: Our study provides a robust signature for predicting patients' prognosis, which might be helpful for therapeutic strategies discovery of LUAD.
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The datasets downloaded for supporting the results of this article are publicly available at the TCGA (https://portal.gdc.cancer.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/).
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The datasets downloaded for supporting the results of this article are publicly available at the TCGA (https://portal.gdc.cancer.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/).
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"Off-context" gene expression in lung cancer identifies a group of metastatic-prone tumors
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570
taxon
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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
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The datasets downloaded for supporting the results of this article are publicly available at the TCGA (https://portal.gdc.cancer.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/).
structure object · 15 fields
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The datasets downloaded for supporting the results of this article are publicly available at the TCGA (https://portal.gdc.cancer.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/).
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sample_count
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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
resolution_check
identifier_resolution_only_no_download_no_licence_read
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licence_read
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[0]
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[1]
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[2]
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[3]
asset:data:geo:GSE50081 licence not read
[4]
asset:data:geo:GSE72094 not downloaded
[5]
asset:data:geo:GSE72094 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
id
method-1
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group_comparison
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wilcoxon
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[0]
group_comparison_wilcoxon
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[0]
two_or_more_groups_continuous
evidence object · 3 fields
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quote
“Kaplan-Meier method was used to draw survival curves. The receiver operating characteristic (ROC) curve was plotted with the SurvivalROC R package. The Wilcoxon test was used to compare the two groups’ differences. The correlation tests were conducted by Pearson correlation analysis. Univariate and multivariate analyses were conducted to determine whether the prognostic model was independently variable when integrated with other clinical factors.” “The TCGA database was used to obtaine the gene expression profile cohort and its corresponding clinical data of LUAD patients, including the FPKM value of gene expression of 535 LUAD samples and 59 normal samples.” “The normalized matrix files of the three cohorts (GSE30219, GSE50081 and GSE72094) from the GEO database were downloaded for the validation data sets.” “Then, Lasso Cox regression was used to selected the most striking markers to establish the prognostic model.”
[1] object · 10 fields
id
method-2
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survival_analysis
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kaplan_meier
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[0]
survival_km
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parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
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high
quote
Kaplan-Meier
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method-3
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[0]
cox_ph
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parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
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quote
Cox regression
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id
method-4
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correlation_analysis
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Correlation analysis
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[0]
pearson_r
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parameters object · 0 fields
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[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
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Pearson correlation
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id
method-5
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Diagnostic test evaluation
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[0]
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[1]
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[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
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[0]
reference_standard_and_test
evidence object · 3 fields
score
0.7
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medium
quote
ROC curve
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gaps array · 1 item
[0]
method.group_comparison_wilcoxon
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
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[0]
meta_analysis
[1]
machine_learning
[2]
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[3]
statistical_regression
[4]
pca
[5]
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[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
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missing_operations array · 1 item
[0]
group_comparison_wilcoxon
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon.
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
reachable
true
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[0]
GSE30219
[1]
GSE50081
[2]
GSE72094
resolved_accessions array · 3 items
[0]
GSE30219
[1]
GSE50081
[2]
GSE72094
statements array · 1 item
[0]
The datasets downloaded for supporting the results of this article are publicly available at the TCGA (https://portal.gdc.cancer.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/).
basis
The paper names GSE30219, GSE50081, GSE72094 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 · 0 items
assets array · 2 items
[0]
source:pmid:34416861
[1]
data:geo:GSE30219
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[0] object · 3 fields
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group_comparison_wilcoxon
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null
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readers array · 0 items
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[0]
data:geo:GSE30219
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review object · 5 fields
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partial
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extraction_review
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lineage object · 4 fields
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evidence array · 1 item
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“Kaplan-Meier method was used to draw survival curves. The receiver operating characteristic (ROC) curve was plotted with the SurvivalROC R package. The Wilcoxon test was used to compare the two groups’ differences. The correlation tests were conducted by Pearson correlation analysis. Univariate and multivariate analyses were conducted to determine whether the prognostic model was independently variable when integrated with other clinical factors.” “The TCGA database was used to obtaine the gene expression profile cohort and its corresponding clinical data of LUAD patients, including the FPKM value of gene expression of 535 LUAD samples and 59 normal samples.” “The normalized matrix files of the three cohorts (GSE30219, GSE50081 and GSE72094) from the GEO database were downloaded for the validation data sets.” “Then, Lasso Cox regression was used to selected the most striking markers to establish the prognostic model.”
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34416861", "kind": "science-record", "revision": 8, "content_hash": "sha256:b268ed87b92c78d13b7eaee87a4d769b063a574ff5fcd46d6c04392a000eda32", "created_at": "2026-11-01T15:41:48Z", "updated_at": "2026-11-01T22:47:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Characteristic of molecular subtypes in lung adenocarcinoma based on m6A RNA methylation modification and immune microenvironment.", "doi": "10.1186/s12885-021-08655-1", "pmid": "34416861", "authors": ["Hao Zhou", "Miaosen Zheng", "Muqi Shi", "Jinjie Wang", "Zhanghao Huang", "Haijian Zhang", "Youlang Zhou", "Jiahai Shi"], "journal": "BMC cancer", "year": 2021, "abstract": "BACKGROUND: Lung adenocarcinoma (LUAD) is a major subtype of lung cancer and closely associated with poor prognosis. N6-methyladenosine (m6A), one of the most predominant modifications in mRNAs, is found to participate in tumorigenesis. However, the potential function of m6A RNA methylation in the tumor immune microenvironment is still murky.\nMETHODS: The gene expression profile cohort and its corresponding clinical data of LUAD patients were downloaded from TCGA database and GEO database. Based on the expression of 21 m6A regulators, we identified two distinct subgroups by consensus clustering. The single-sample gene-set enrichment analysis (ssGSEA) algorithm was conducted to quantify the relative abundance of the fraction of 28 immune cell types. The prognostic model was constructed by Lasso Cox regression. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate the prognostic model.\nRESULT: Consensus classification separated the patients into two clusters (clusters 1 and 2). Those patients in cluster 1 showed a better prognosis and were related to higher immune scores and more immune cell infiltration. Subsequently, 457 differentially expressed genes (DEGs) between the two clusters were identified, and then a seven-gene prognostic model was constricted. The survival analysis showed poor prognosis in patients with high-risk score. The ROC curve confirmed the predictive accuracy of this prognostic risk signature. Besides, further analysis indicated that there were significant differences between the high-risk and low-risk groups in stages, status, clustering subtypes, and immunoscore. Low-risk group was related to higher immune score, more immune cell infiltration, and lower clinical stages. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. Ultimately, the efficacy of this prognostic model was successfully validated in several external cohorts (GSE30219, GSE50081 and GSE72094).\nCONCLUSION: Our study provides a robust signature for predicting patients' prognosis, which might be helpful for therapeutic strategies discovery of LUAD.", "claims": [{"id": "claim-data-access", "statement": "The datasets downloaded for supporting the results of this article are publicly available at the TCGA (https://portal.gdc.cancer.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34416861", "locator": "sections[27] \"notes\" paragraph 1", "quote": "The datasets downloaded for supporting the results of this article are publicly available at the TCGA (https://portal.gdc.cancer.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:34416861"], "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:GSE30219"], "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_wilcoxon", "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:GSE30219"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34416861", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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