Integrated analysis of necroptosis-related lncRNAs for prognosis and immunotherapy of patients with pancreatic adenocarcinoma

Accumulating studies have revealed that necroptosis plays a vital role in the occurrence and development of pancreatic adenocarcinoma (PAAD). We aimed to construct a prognostic model for PAAD on the basis of necroptosis-related lncRNAs (NRLs). A coexpression network between necroptosis-related mRNAs...

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Main Authors: Jiantao Mo, Zhiwei Cui, Qiqi Wang, Weifan Zhang, Jie Li, Shuai Wu, Weikun Qian, Cancan Zhou, Qingyong Ma, Zheng Wang, Zheng Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.940794/full
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author Jiantao Mo
Zhiwei Cui
Qiqi Wang
Weifan Zhang
Jie Li
Shuai Wu
Weikun Qian
Cancan Zhou
Qingyong Ma
Zheng Wang
Zheng Wu
author_facet Jiantao Mo
Zhiwei Cui
Qiqi Wang
Weifan Zhang
Jie Li
Shuai Wu
Weikun Qian
Cancan Zhou
Qingyong Ma
Zheng Wang
Zheng Wu
author_sort Jiantao Mo
collection DOAJ
description Accumulating studies have revealed that necroptosis plays a vital role in the occurrence and development of pancreatic adenocarcinoma (PAAD). We aimed to construct a prognostic model for PAAD on the basis of necroptosis-related lncRNAs (NRLs). A coexpression network between necroptosis-related mRNAs and NRLs based on The Cancer Genome Atlas (TCGA) was constructed. Then, differentially expressed necroptosis-related lncRNAs (DENRLs) were screened from TCGA and Genotype-Tissue Expression project (GTEx) datasets. Univariate Cox regression (uni-Cox) analysis was performed on these DENRLs to identify lncRNAs significantly correlated with prognosis. Least absolute shrinkage and selection operator (LASSO) regression was performed for preventing overfitting on these lncRNAs. Multivariate Cox analysis (multi-Cox) was performed to establish a risk model based on lncRNAs that served as an independent prognostic factor. Next, the Kaplan–Meier analysis, time-dependent receiver operating characteristics (ROC), uni-Cox, multi-Cox regression, nomogram, and calibration curves were constructed to support the accuracy of the model. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were also performed on risk groups, and it was found that the low-risk group was closely correlated with immune infiltration and immunotherapy. To further evaluate the immune differences between different clusters, we divided the patients into two clusters. Cluster 2 was more significantly infiltrated with immune cells and had higher immune scores. These results shed new light on the pathogenesis of PAAD based on NRLs and develop a prognostic model for diagnosing and guiding personalized immunotherapy of PAAD patients.
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spelling doaj.art-dc7222f190d8463b8c576f1aeebd7da32022-12-22T03:44:24ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.940794940794Integrated analysis of necroptosis-related lncRNAs for prognosis and immunotherapy of patients with pancreatic adenocarcinomaJiantao Mo0Zhiwei Cui1Qiqi Wang2Weifan Zhang3Jie Li4Shuai Wu5Weikun Qian6Cancan Zhou7Qingyong Ma8Zheng Wang9Zheng Wu10Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaAccumulating studies have revealed that necroptosis plays a vital role in the occurrence and development of pancreatic adenocarcinoma (PAAD). We aimed to construct a prognostic model for PAAD on the basis of necroptosis-related lncRNAs (NRLs). A coexpression network between necroptosis-related mRNAs and NRLs based on The Cancer Genome Atlas (TCGA) was constructed. Then, differentially expressed necroptosis-related lncRNAs (DENRLs) were screened from TCGA and Genotype-Tissue Expression project (GTEx) datasets. Univariate Cox regression (uni-Cox) analysis was performed on these DENRLs to identify lncRNAs significantly correlated with prognosis. Least absolute shrinkage and selection operator (LASSO) regression was performed for preventing overfitting on these lncRNAs. Multivariate Cox analysis (multi-Cox) was performed to establish a risk model based on lncRNAs that served as an independent prognostic factor. Next, the Kaplan–Meier analysis, time-dependent receiver operating characteristics (ROC), uni-Cox, multi-Cox regression, nomogram, and calibration curves were constructed to support the accuracy of the model. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were also performed on risk groups, and it was found that the low-risk group was closely correlated with immune infiltration and immunotherapy. To further evaluate the immune differences between different clusters, we divided the patients into two clusters. Cluster 2 was more significantly infiltrated with immune cells and had higher immune scores. These results shed new light on the pathogenesis of PAAD based on NRLs and develop a prognostic model for diagnosing and guiding personalized immunotherapy of PAAD patients.https://www.frontiersin.org/articles/10.3389/fgene.2022.940794/fullpancreatic adenocarcinomanecroptosis-related lncRNAsrisk modelprognostic biomarkersimmunotherapy
spellingShingle Jiantao Mo
Zhiwei Cui
Qiqi Wang
Weifan Zhang
Jie Li
Shuai Wu
Weikun Qian
Cancan Zhou
Qingyong Ma
Zheng Wang
Zheng Wu
Integrated analysis of necroptosis-related lncRNAs for prognosis and immunotherapy of patients with pancreatic adenocarcinoma
Frontiers in Genetics
pancreatic adenocarcinoma
necroptosis-related lncRNAs
risk model
prognostic biomarkers
immunotherapy
title Integrated analysis of necroptosis-related lncRNAs for prognosis and immunotherapy of patients with pancreatic adenocarcinoma
title_full Integrated analysis of necroptosis-related lncRNAs for prognosis and immunotherapy of patients with pancreatic adenocarcinoma
title_fullStr Integrated analysis of necroptosis-related lncRNAs for prognosis and immunotherapy of patients with pancreatic adenocarcinoma
title_full_unstemmed Integrated analysis of necroptosis-related lncRNAs for prognosis and immunotherapy of patients with pancreatic adenocarcinoma
title_short Integrated analysis of necroptosis-related lncRNAs for prognosis and immunotherapy of patients with pancreatic adenocarcinoma
title_sort integrated analysis of necroptosis related lncrnas for prognosis and immunotherapy of patients with pancreatic adenocarcinoma
topic pancreatic adenocarcinoma
necroptosis-related lncRNAs
risk model
prognostic biomarkers
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fgene.2022.940794/full
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