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pmid:32924987

Identification of a novel CpG methylation signature to predict prognosis in lung squamous cell carcinoma.

Nan Lee · Xuelian Xia · Hui Meng · Weiliang Zhu · Xiankai Wang · Tianyuan Zhang · Chanyuan Zhang · Jian Zhang · Peng Luo

Cancer biomarkers : section A of Disease markers · 2021 doi:10.3233/CBM-201564

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Identification of a novel CpG methylation signature to predict prognosis in lung squamous cell carcinoma.
doi
10.3233/CBM-201564
pmid
32924987
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[0]
Nan Lee
[1]
Xuelian Xia
[2]
Hui Meng
[3]
Weiliang Zhu
[4]
Xiankai Wang
[5]
Tianyuan Zhang
[6]
Chanyuan Zhang
[7]
Jian Zhang
[8]
Peng Luo
journal
Cancer biomarkers : section A of Disease markers
year
2021
abstract
BACKGROUND: DNA methylation plays a vital role in modulating genomic function and warrants evaluation as a biomarker for the diagnosis and treatment of lung squamous cell carcinoma (LUSC). OBJECTIVE: In this study, we aimed to identify effective potential biomarkers for predicting prognosis and drug sensitivity in LUSC. METHODS: A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO). RESULTS: A methylated region consisting of 3 sites (cg06675147, cg07064331, cg20429172) was selected. Patients were divided into a high-risk group and a low-risk group in the training dataset. High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82-4.07, P< 0.001) compared with low-risk patients. The accuracy of the prognostic signature was validated in the test and validation cohorts (TCGA, n= 94; GSE56044, n= 23). Gene set variation analysis (GSVA) showed that activity in the cell cycle/mitotic, ERBB, and ERK/MAPK pathways was higher in the high-risk compared with the low-risk group, which may lead to differences in OS.Interestingly, we observed that patients in the high-risk group were more sensitive to gemcitabine and docetaxel than the low-risk group, which is consistent with results of the GSVA. CONCLUSION: We report novel methylation sites that could be used as powerful tools for predicting risk factors for poorer survival in patients with LUSC.
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A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).
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A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).
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A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).
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A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).
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High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82–4.07, P< 0.001) compared with low-risk patients.
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High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82–4.07, P< 0.001) compared with low-risk patients.
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Genome-wide DNA methylation analysis of lung carcinoma
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A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).
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A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).
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A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32924987", "kind": "science-record", "revision": 3, "content_hash": "sha256:d19380b43ccfc5b697a432a795cf9730b8fa9ecbfb0762fd27a141da979b44ce", "created_at": "2026-11-01T17:34:05Z", "updated_at": "2026-11-01T21:23:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a novel CpG methylation signature to predict prognosis in lung squamous cell carcinoma.", "doi": "10.3233/CBM-201564", "pmid": "32924987", "authors": ["Nan Lee", "Xuelian Xia", "Hui Meng", "Weiliang Zhu", "Xiankai Wang", "Tianyuan Zhang", "Chanyuan Zhang", "Jian Zhang", "Peng Luo"], "journal": "Cancer biomarkers : section A of Disease markers", "year": 2021, "abstract": "BACKGROUND: DNA methylation plays a vital role in modulating genomic function and warrants evaluation as a biomarker for the diagnosis and treatment of lung squamous cell carcinoma (LUSC).\nOBJECTIVE: In this study, we aimed to identify effective potential biomarkers for predicting prognosis and drug sensitivity in LUSC.\nMETHODS: A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).\nRESULTS: A methylated region consisting of 3 sites (cg06675147, cg07064331, cg20429172) was selected. Patients were divided into a high-risk group and a low-risk group in the training dataset. High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82-4.07, P< 0.001) compared with low-risk patients. The accuracy of the prognostic signature was validated in the test and validation cohorts (TCGA, n= 94; GSE56044, n= 23). Gene set variation analysis (GSVA) showed that activity in the cell cycle/mitotic, ERBB, and ERK/MAPK pathways was higher in the high-risk compared with the low-risk group, which may lead to differences in OS.Interestingly, we observed that patients in the high-risk group were more sensitive to gemcitabine and docetaxel than the low-risk group, which is consistent with results of the GSVA.\nCONCLUSION: We report novel methylation sites that could be used as powerful tools for predicting risk factors for poorer survival in patients with LUSC.", "claims": [{"id": "claim-method", "statement": "A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32924987", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32924987", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82–4.07, P< 0.001) compared with low-risk patients.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82–4.07, P< 0.001) compared with low-risk patients."}, "evidence": [{"asset": "source:pmid:32924987", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82–4.07, P< 0.001) compared with low-risk patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82–4.07, P< 0.001) compared with low-risk patients.", "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:32924987"], "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:GSE56044"], "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:GSE56044"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32924987", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3233/CBM-201564", "sha256": "sha256:5f07833a38aef783a4127ca32e880f8e1abe0fbb16cb94b843819da0e9af3def", "bytes": 1650, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3233/CBM-201564", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12499960", "source": "ncbi_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE56044", "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=GSE56044", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE56044", "version": null, "note": "A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1351866", "GSM1351867", "GSM1351868", "GSM1351869", "GSM1351870", "GSM1351871", "GSM1351872", "GSM1351873", "GSM1351874", "GSM1351875", "GSM1351876", "GSM1351877", "GSM1351878", "GSM1351879", "GSM1351880", "GSM1351881", "GSM1351882", "GSM1351883", "GSM1351884", "GSM1351885", "GSM1351886", "GSM1351887", "GSM1351888", "GSM1351889", "GSM1351890", "GSM1351891", "GSM1351892", "GSM1351893", "GSM1351894", "GSM1351895", "GSM1351896", "GSM1351897", "GSM1351898", "GSM1351899", "GSM1351900", "GSM1351901", "GSM1351902", "GSM1351903", "GSM1351904", "GSM1351905", "GSM1351906", "GSM1351907", "GSM1351908", "GSM1351909", "GSM1351910", "GSM1351911", "GSM1351912", "GSM1351913", "GSM1351914", "GSM1351915", "GSM1351916", "GSM1351917", "GSM1351918", "GSM1351919", "GSM1351920", "GSM1351921", "GSM1351922", "GSM1351923", "GSM1351924", "GSM1351925", "GSM1351926", "GSM1351927", "GSM1351928", "GSM1351929", "GSM1351930", "GSM1351931", "GSM1351932", "GSM1351933", "GSM1351934", "GSM1351935", "GSM1351936", "GSM1351937", "GSM1351938", "GSM1351939", "GSM1351940", "GSM1351941", "GSM1351942", "GSM1351943", "GSM1351944", "GSM1351945", "GSM1351946", "GSM1351947", "GSM1351948", "GSM1351949", "GSM1351950", "GSM1351951", "GSM1351952", "GSM1351953", "GSM1351954", "GSM1351955", "GSM1351956", "GSM1351957", "GSM1351958", "GSM1351959", "GSM1351960", "GSM1351961", "GSM1351962", "GSM1351963", "GSM1351964", "GSM1351965", "GSM1351966", "GSM1351967", "GSM1351968", "GSM1351969", "GSM1351970", "GSM1351971", "GSM1351972", "GSM1351973", "GSM1351974", "GSM1351975", "GSM1351976", "GSM1351977", "GSM1351978", "GSM1351979", "GSM1351980", "GSM1351981", "GSM1351982", "GSM1351983", "GSM1351984", "GSM1351985", "GSM1351986", "GSM1351987", "GSM1351988", "GSM1351989", "GSM1351990", "GSM1351991", "GSM1351992", "GSM1351993", "GSM1351994", "GSM1351995", "GSM1351996", "GSM1351997", "GSM1351998", "GSM1351999", "GSM1352000", "GSM1352001"], "sample_count": 136, "group_sizes": null, "group_sizes_basis": null, "platform": "13534", "taxon": "Homo sapiens", "title": "Genome-wide DNA methylation analysis of lung carcinoma ", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE56044 not downloaded", "asset:data:geo:GSE56044 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO)."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 0.001, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. 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