Identification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma

Abstract The aim of this paper was to identify DNA methylation based biomarkers for predicting overall survival (OS) of stage I–II lung adenocarcinoma (LUAD) patients. Methylation profile data of patients with stage I–II LUAD from The Cancer Genome Atlas (TCGA) database was used to determine methyla...

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Autores principales:	Heng Wang, Chuangye Wei, Peng Pan, Fengfeng Yuan, Jiancheng Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1301d628903c4a03b886f66f5ad0bc8f
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spelling	oai:doaj.org-article:1301d628903c4a03b886f66f5ad0bc8f2021-12-02T14:35:34ZIdentification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma10.1038/s41598-021-89429-42045-2322https://doaj.org/article/1301d628903c4a03b886f66f5ad0bc8f2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89429-4https://doaj.org/toc/2045-2322Abstract The aim of this paper was to identify DNA methylation based biomarkers for predicting overall survival (OS) of stage I–II lung adenocarcinoma (LUAD) patients. Methylation profile data of patients with stage I–II LUAD from The Cancer Genome Atlas (TCGA) database was used to determine methylation sites-based hallmark for stage I–II LUAD patients’ OS. The patients were separated into training and validation datasets by using median risk score as cutoff. Univariate Cox, least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were employed to develop a DNA methylation signature for OS of patients with stage I–II LUAD. As a result, an 11-DNA methylation signature was determined to be critically associated with the OS of patients with stage I–II LUAD. Analysis of receiver operating characteristics (ROC) suggested a high prognostic effectiveness of the 11-DNA methylation signature in patients with stage I–II LUAD (AUC at 1, 3, 5 years in training set were (0.849, 0.879, 0.831, respectively), validation set (0.742, 0.807, 0.904, respectively), entire TCGA dataset (0.747, 0.818, 0.870, respectively). Kaplan–Meier survival analyses exhibited that survival was significantly longer in the low-risk cohort compared to the high-risk cohort in the training dataset (P = 7e − 07), in the validation dataset (P = 1e − 08), and in the all-cohort dataset (P = 6e − 14). In addition, a nomogram was developed based on molecular factor (methylation risk score) as well as clinical factors (age and cancer status) (AUC at 1, 3, 5 years entire TCGA dataset were 0.770, 0.849, 0.979, respectively). The result verified that our methylomics-associated nomogram had a strong robustness for predicting stage I–II LUAD patients’ OS. Furthermore, the nomogram combined clinical and molecular factors to determine an individualized probability of recurrence for patients with stage I–II LUAD, which stood for a major advance in the field of personalized medicine for pulmonary oncology. Collectively, we successfully identified a DNA methylation biomarker and a DNA methylation-based nomogram to predict the OS of patients with stage I–II LUAD.Heng WangChuangye WeiPeng PanFengfeng YuanJiancheng ChengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heng Wang Chuangye Wei Peng Pan Fengfeng Yuan Jiancheng Cheng Identification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma
description	Abstract The aim of this paper was to identify DNA methylation based biomarkers for predicting overall survival (OS) of stage I–II lung adenocarcinoma (LUAD) patients. Methylation profile data of patients with stage I–II LUAD from The Cancer Genome Atlas (TCGA) database was used to determine methylation sites-based hallmark for stage I–II LUAD patients’ OS. The patients were separated into training and validation datasets by using median risk score as cutoff. Univariate Cox, least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were employed to develop a DNA methylation signature for OS of patients with stage I–II LUAD. As a result, an 11-DNA methylation signature was determined to be critically associated with the OS of patients with stage I–II LUAD. Analysis of receiver operating characteristics (ROC) suggested a high prognostic effectiveness of the 11-DNA methylation signature in patients with stage I–II LUAD (AUC at 1, 3, 5 years in training set were (0.849, 0.879, 0.831, respectively), validation set (0.742, 0.807, 0.904, respectively), entire TCGA dataset (0.747, 0.818, 0.870, respectively). Kaplan–Meier survival analyses exhibited that survival was significantly longer in the low-risk cohort compared to the high-risk cohort in the training dataset (P = 7e − 07), in the validation dataset (P = 1e − 08), and in the all-cohort dataset (P = 6e − 14). In addition, a nomogram was developed based on molecular factor (methylation risk score) as well as clinical factors (age and cancer status) (AUC at 1, 3, 5 years entire TCGA dataset were 0.770, 0.849, 0.979, respectively). The result verified that our methylomics-associated nomogram had a strong robustness for predicting stage I–II LUAD patients’ OS. Furthermore, the nomogram combined clinical and molecular factors to determine an individualized probability of recurrence for patients with stage I–II LUAD, which stood for a major advance in the field of personalized medicine for pulmonary oncology. Collectively, we successfully identified a DNA methylation biomarker and a DNA methylation-based nomogram to predict the OS of patients with stage I–II LUAD.
format	article
author	Heng Wang Chuangye Wei Peng Pan Fengfeng Yuan Jiancheng Cheng
author_facet	Heng Wang Chuangye Wei Peng Pan Fengfeng Yuan Jiancheng Cheng
author_sort	Heng Wang
title	Identification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma
title_short	Identification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma
title_full	Identification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma
title_fullStr	Identification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma
title_full_unstemmed	Identification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma
title_sort	identification of a methylomics-associated nomogram for predicting overall survival of stage i–ii lung adenocarcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1301d628903c4a03b886f66f5ad0bc8f
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Identification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma

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