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
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Publicado: Nature Portfolio 2021
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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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