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pmid:34285141

Development and validation of a novel epigenetic-related prognostic signature and candidate drugs for patients with lung adenocarcinoma.

Zhihao Wang · Kidane Siele Embaye · Qing Yang · Lingzhi Qin · Chao Zhang · Liwei Liu · Xiaoqian Zhan · Fengdi Zhang · Xi Wang · Shenghui Qin

Aging · 2021 doi:10.18632/aging.203315

Paper

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Experiment

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Data

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Development and validation of a novel epigenetic-related prognostic signature and candidate drugs for patients with lung adenocarcinoma.
doi
10.18632/aging.203315
pmid
34285141
authors array · 10 items
[0]
Zhihao Wang
[1]
Kidane Siele Embaye
[2]
Qing Yang
[3]
Lingzhi Qin
[4]
Chao Zhang
[5]
Liwei Liu
[6]
Xiaoqian Zhan
[7]
Fengdi Zhang
[8]
Xi Wang
[9]
Shenghui Qin
journal
Aging
year
2021
abstract
BACKGROUND: Epigenetic dysregulation has been increasingly proposed as a hallmark of cancer. Here, the aim of this study is to establish an epigenetic-related signature for predicting the prognosis of lung adenocarcinoma (LUAD) patients. RESULTS: Five epigenetic-related genes (ERGs) (ARRB1, PARP1, PKM, TFDP1, and YWHAZ) were identified as prognostic hub genes and used to establish a prognostic signature. According our risk score system, LUAD patients were stratified into high and low risk groups, and patients in the high risk group had a worse prognosis. ROC analysis indicated that the signature was precise in predicting the prognosis. A new nomogram was constructed based on the five hub genes, which can predict the OS of every LUAD patients. The calibration curves showed that the nomogram had better accuracy in prediction. Finally, candidate drugs that aimed at hub ERGs were identified, which included 47 compounds. CONCLUSIONS: Our epigenetic-related signature nomogram can effectively and reliably predict OS of LUAD patients, also we provide precise targeted chemotherapeutic drugs. METHODS: The genomic data and clinical data of LUAD cohort were downloaded from the TCGA database and ERGs were obtained from the EpiFactors database. GSE31210 and GSE50081 microarray datasets were included as independent external datasets. Univariate Cox, LASSO regression, and multivariate Cox analyses were applied to construct the epigenetic-related signature.
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Univariate and multivariate Cox regression analyses of OS in LUAD patients.
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section_index
5
section_title
Identification of survival-related differentially expressed ERGs
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column_count
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table object · 8 fields
label
Table 1
caption
Univariate and multivariate Cox regression analyses of OS in LUAD patients.
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[0] array · 6 items
[0]
Genes
[1]
Univariate analysis
[2]
P
[3]
Multivariate analysis
[4]
P
[5]
Coef
[1] array · 2 items
[0]
HR (95% CI)
[1]
HR (95% CI)
[2] array · 6 items
[0]
ARRB1
[1]
0.9512(0.9180-0.9857)
[2]
0.0059
[3]
0.9636(0.9318-0.9965)
[4]
0.0306
[5]
-0.0371
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PARP1
[1]
1.0158(1.0021-1.0299)
[2]
0.0238
[3]
1.0156(1.0020-1.0294)
[4]
0.0251
[5]
0.0155
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PKM
[1]
1.0049(1.0027-1.0072)
[2]
<0.0001
[3]
1.0043(1.0018-1.0068)
[4]
0.0007
[5]
0.0043
[5] array · 6 items
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TFDP1
[1]
1.0012(1.0001-1.0023)
[2]
0.0266
[3]
1.0011(0.9999-1.0023)
[4]
0.0665
[5]
0.0011
[6] array · 6 items
[0]
YWHAZ
[1]
1.0058(1.0027-1.0090)
[2]
0.0002
[3]
1.0045(1.0021-1.0078)
[4]
0.0070
[5]
0.0045
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HJURP
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1.0553(1.0188-1.0930)
[2]
0.0027
[3]
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ACTL6A
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1.0231(1.0056-1.0409)
[2]
0.0096
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1.0109(1.0000-1.0215)
[2]
0.0409
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CDK1
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1.0190(1.0019-1.0363)
[2]
0.0289
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[1]
0.8885(0.8037-0.9822)
[2]
0.0209
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[1]
1.0366(1.0092-1.0647)
[2]
0.0086
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1.0457(1.0010-1.0826)
[2]
0.0117
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[1]
1.0216(1.0012-1.0423)
[2]
0.0375
[15] array · 3 items
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1.0740(1.0163-1.1350)
[2]
0.0113
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[0]
AURKA
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1.0243(1.0063-1.0426)
[2]
0.0079
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PRKDC
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1.0194(1.0048-1.0342)
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0.0091
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section[5]/table-wrap[1]#t1
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Relationship between the expression of epigenetic-related genes and clinical characteristics.
structure object · 5 fields
pmcid
PMC8351720
section_index
7
section_title
Relationships between risk score and clinicopathological factors
row_count
8
column_count
7
table object · 8 fields
label
Table 2
caption
Relationship between the expression of epigenetic-related genes and clinical characteristics.
rows array · 8 items
[0] array · 7 items
[0]
Gene symbol
[1]
Age (≥65/<65)
[2]
Gender (male/female)
[3]
Pathological stage (IV-III/ I–II)
[4]
T stage (T3–T4/T1–T2)
[5]
N stage (N2–3/N0-N1)
[6]
M stage (M1/ M0)
[1] array · 6 items
[0]
t(P)
[1]
t(P)
[2]
t(P)
[3]
t(P)
[4]
t(P)
[5]
t(P)
[2] array · 7 items
[0]
ARRB1
[1]
-1.513(0.131)
[2]
-1.635(0.103)
[3]
1.487(0.139)
[4]
0.507(0.614)
[5]
1.17(0.243)
[6]
0.395(0.697)
[3] array · 7 items
[0]
PARP1
[1]
0.934(0.351)
[2]
-0.761(0.447)
[3]
-0.344(0.732)
[4]
-0.269(0.789)
[5]
-0.628(0.531)
[6]
-1.23(0.233)
[4] array · 7 items
[0]
YWHAZ
[1]
0.369(0.713)
[2]
-1.728(0.085)
[3]
-2.189(0.031)
[4]
-1.72(0.092)
[5]
-1.302(0.194)
[6]
-0.694(0.495)
[5] array · 7 items
[0]
TFDP1
[1]
1.113(0.267)
[2]
-1.077(0.283)
[3]
-1.035(0.304)
[4]
1.155(0.249)
[5]
-1.083(0.281)
[6]
-1.029(0.316)
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[0]
PKM
[1]
-1.609(0.109)
[2]
-0.663(0.508)
[3]
-2.865(0.005)
[4]
-1.936(0.059)
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-3.006(0.003)
[6]
-1.352(0.191)
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riskScore
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0.612(0.541)
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-1.205(0.229)
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-3.031(0.003)
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-2.092(0.042)
[5]
-2.704(0.008)
[6]
-1.997(0.060)
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section[7]/table-wrap[1]#t2
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The comparison of two paired groups was performed using the Wilcoxon rank-sum test.
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group_comparison_wilcoxon
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The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon.
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tier
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GSE31210
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GSE31210
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GSE50081
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The RNA-seq data of 497 LUAD and 54 normal lung samples were downloaded from The Cancer Genome Atlas (TCGA) database, and the RNA-seq data of 174 LUAD and 127 LUAD samples were downloaded from GSE31210 and GSE50081 dataset, respectively.
basis
The paper names GSE31210, GSE50081 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34285141", "kind": "science-record", "revision": 8, "content_hash": "sha256:3099b6ebfed34a06447c5394d81f8b94b07a27099909854c1436fb9eeb496cfa", "created_at": "2026-11-01T15:41:44Z", "updated_at": "2026-11-01T22:04:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development and validation of a novel epigenetic-related prognostic signature and candidate drugs for patients with lung adenocarcinoma.", "doi": "10.18632/aging.203315", "pmid": "34285141", "authors": ["Zhihao Wang", "Kidane Siele Embaye", "Qing Yang", "Lingzhi Qin", "Chao Zhang", "Liwei Liu", "Xiaoqian Zhan", "Fengdi Zhang", "Xi Wang", "Shenghui Qin"], "journal": "Aging", "year": 2021, "abstract": "BACKGROUND: Epigenetic dysregulation has been increasingly proposed as a hallmark of cancer. Here, the aim of this study is to establish an epigenetic-related signature for predicting the prognosis of lung adenocarcinoma (LUAD) patients.\nRESULTS: Five epigenetic-related genes (ERGs) (ARRB1, PARP1, PKM, TFDP1, and YWHAZ) were identified as prognostic hub genes and used to establish a prognostic signature. According our risk score system, LUAD patients were stratified into high and low risk groups, and patients in the high risk group had a worse prognosis. ROC analysis indicated that the signature was precise in predicting the prognosis. A new nomogram was constructed based on the five hub genes, which can predict the OS of every LUAD patients. The calibration curves showed that the nomogram had better accuracy in prediction. Finally, candidate drugs that aimed at hub ERGs were identified, which included 47 compounds.\nCONCLUSIONS: Our epigenetic-related signature nomogram can effectively and reliably predict OS of LUAD patients, also we provide precise targeted chemotherapeutic drugs.\nMETHODS: The genomic data and clinical data of LUAD cohort were downloaded from the TCGA database and ERGs were obtained from the EpiFactors database. GSE31210 and GSE50081 microarray datasets were included as independent external datasets. Univariate Cox, LASSO regression, and multivariate Cox analyses were applied to construct the epigenetic-related signature.", "claims": [{"id": "claim-method", "statement": "The comparison of two paired groups was performed using the Wilcoxon rank-sum test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34285141", "locator": "sections[19] \"Statistical analysis\" paragraph 2", "quote": "The comparison of two paired groups was performed using the Wilcoxon rank-sum test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The RNA-seq data of 497 LUAD and 54 normal lung samples were downloaded from The Cancer Genome Atlas (TCGA) database, and the RNA-seq data of 174 LUAD and 127 LUAD samples were downloaded from GSE31210 and GSE50081 dataset, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34285141", "locator": "sections[13] \"Study subjects\" paragraph 2", "quote": "The RNA-seq data of 497 LUAD and 54 normal lung samples were downloaded from The Cancer Genome Atlas (TCGA) database, and the RNA-seq data of 174 LUAD and 127 LUAD samples were downloaded from GSE31210 and GSE50081 dataset, respectively."}], "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:34285141"], "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:GSE31210"], "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:GSE31210"], "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:34285141", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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