N6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, fatal tumor. N6-methylandenosine (m6A) methylation is the major epigenetic modification of RNA including lncRNAs. The roles of m6A-related lncRNAs in PDAC have not been fully clarified. This study aims to assess gene signatures...

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Autores principales:	YuHai Hu, YiPing Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/05836a8337c04300898dd9081f967c4c
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spelling	oai:doaj.org-article:05836a8337c04300898dd9081f967c4c2021-12-02T19:12:33ZN6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma10.1038/s41598-021-97362-92045-2322https://doaj.org/article/05836a8337c04300898dd9081f967c4c2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97362-9https://doaj.org/toc/2045-2322Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, fatal tumor. N6-methylandenosine (m6A) methylation is the major epigenetic modification of RNA including lncRNAs. The roles of m6A-related lncRNAs in PDAC have not been fully clarified. This study aims to assess gene signatures and prognostic value of m6A-related lncRNAs in PDAC. The Cancer Genome Atlas (TCGA) dataset and the International Cancer Genome Consortium (ICGC) dataset were explored to identify m6A-related lncRNAs. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were performed to construct the m6A-related lncRNAs prognostic riskscore (m6A-LPR) model to predict the overall survival (OS) in the TCGA training cohort. Kaplan–Meier curve with log-rank test and receiver operating characteristic (ROC) curve were used to evaluate the prognostic value of the m6A-LPR. Furthermore, the robustness of the m6A-LPR was further validated in the ICGC cohort. Tumor immunity was evaluated using ESTIMATE and CIBERSORT algorithms. A total of 262 m6A-related lncRNAs were identified in two datasets. In the TCGA training cohort, 28 prognostic m6A-related lncRNAs were identified and the m6A-LPR including four m6A-related lncRNAs was constructed. The m6A-LPR was able to identify high-risk patients with significantly poorer OS and accurately predict OS in both the TCGA training cohort and the ICGC validation cohort. Analysis of tumor immunity revealed that high-risk groups had remarkably lower stromal, immune, and ESTIMATE scores. Moreover, high-risk groups were associated with significantly higher levels of plasma B cells and resting NK cells infiltration, and lower levels of infiltrating resting memory CD4 T cells, monocytes, and resting mast cells. Our study proposed a robust m6A-related prognostic signature of lncRNAs for predicting OS in PDAC, which provides some clues for further studies focusing on the mechanism process underlying m6A modification of lncRNAs.YuHai HuYiPing ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q YuHai Hu YiPing Chen N6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma
description	Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, fatal tumor. N6-methylandenosine (m6A) methylation is the major epigenetic modification of RNA including lncRNAs. The roles of m6A-related lncRNAs in PDAC have not been fully clarified. This study aims to assess gene signatures and prognostic value of m6A-related lncRNAs in PDAC. The Cancer Genome Atlas (TCGA) dataset and the International Cancer Genome Consortium (ICGC) dataset were explored to identify m6A-related lncRNAs. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were performed to construct the m6A-related lncRNAs prognostic riskscore (m6A-LPR) model to predict the overall survival (OS) in the TCGA training cohort. Kaplan–Meier curve with log-rank test and receiver operating characteristic (ROC) curve were used to evaluate the prognostic value of the m6A-LPR. Furthermore, the robustness of the m6A-LPR was further validated in the ICGC cohort. Tumor immunity was evaluated using ESTIMATE and CIBERSORT algorithms. A total of 262 m6A-related lncRNAs were identified in two datasets. In the TCGA training cohort, 28 prognostic m6A-related lncRNAs were identified and the m6A-LPR including four m6A-related lncRNAs was constructed. The m6A-LPR was able to identify high-risk patients with significantly poorer OS and accurately predict OS in both the TCGA training cohort and the ICGC validation cohort. Analysis of tumor immunity revealed that high-risk groups had remarkably lower stromal, immune, and ESTIMATE scores. Moreover, high-risk groups were associated with significantly higher levels of plasma B cells and resting NK cells infiltration, and lower levels of infiltrating resting memory CD4 T cells, monocytes, and resting mast cells. Our study proposed a robust m6A-related prognostic signature of lncRNAs for predicting OS in PDAC, which provides some clues for further studies focusing on the mechanism process underlying m6A modification of lncRNAs.
format	article
author	YuHai Hu YiPing Chen
author_facet	YuHai Hu YiPing Chen
author_sort	YuHai Hu
title	N6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma
title_short	N6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma
title_full	N6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma
title_fullStr	N6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma
title_full_unstemmed	N6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma
title_sort	n6-methylandenosine-related lncrnas play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/05836a8337c04300898dd9081f967c4c
work_keys_str_mv	AT yuhaihu n6methylandenosinerelatedlncrnasplayanimportantroleintheprognosisandimmunemicroenvironmentofpancreaticductaladenocarcinoma AT yipingchen n6methylandenosinerelatedlncrnasplayanimportantroleintheprognosisandimmunemicroenvironmentofpancreaticductaladenocarcinoma
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N6-methylandenosine-related lncRNAs play an important role in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma

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