Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade glioma

Accumulating evidence reveals that ferroptosis and pyroptosis play pivotal roles in tumorigenesis of low-grade glioma (LGG). In this research, we aimed to classify molecular subtypes and further identify and verify a novel multigene signature in LGG on the basis of ferroptosis and pyroptosis-relate...

Full description

Bibliographic Details
Main Authors: Jie Wang, Jie Ren, Jifeng Liu, Linyun Zhang, Qihang Yuan, Bin Dong
Format: Article
Language:English
Published: Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2022-09-01
Series:Biomolecules & Biomedicine
Subjects:
Online Access:https://www.bjbms.org/ojs/index.php/bjbms/article/view/6888
_version_ 1797261314970615808
author Jie Wang
Jie Ren
Jifeng Liu
Linyun Zhang
Qihang Yuan
Bin Dong
author_facet Jie Wang
Jie Ren
Jifeng Liu
Linyun Zhang
Qihang Yuan
Bin Dong
author_sort Jie Wang
collection DOAJ
description Accumulating evidence reveals that ferroptosis and pyroptosis play pivotal roles in tumorigenesis of low-grade glioma (LGG). In this research, we aimed to classify molecular subtypes and further identify and verify a novel multigene signature in LGG on the basis of ferroptosis and pyroptosis-related genes (FPRGs). Raw sequencing data and corresponding clinical data of LGG samples retrieved from the TCGA and CGGA databases were obtained for the training and validation datasets. Non-negative matrix factorization (NMF) clustering defined by FPRGs associated with prognosis was performed to classify molecular subtypes of LGG patients. LASSO-SVM-Random Forest analysis was carried out to develop an FPRG signature to predict the survival and benefit of immunotherapy of LGG patients. NMF clustering defined by FPRGs with prognostic values acted to categorize LGG patients into two molecular subtypes with different prognosis, clinical traits and immune microenvironments. A six-FPRG prognostic signature was constructed, accompanied by the optimal p-value. The AUC values of our signature exhibited great prognostic performances. Our signature was superior to other four well-recognized signatures in predicting the survival probability of LGG patients. Immune characteristics, tumor mutation profile, tumor stemness indices, MGMT methylation and immunotherapy response biomarkers showed significant differences between high- and low-risk populations. Finally, a nomogram was created for quantitative prediction of the survival probability of LGG patients, with the AUC values of the nomogram being 0.916, 0.888 and 0.836 for 1-, 3- and 5-year survival, sequentially. Overall, the FPRG signature may function as an effective indicator for the prognosis prediction and immunotherapy response of LGG patients.
first_indexed 2024-04-24T23:39:15Z
format Article
id doaj.art-afc118dcc5fe45fa857f5e09992bb15d
institution Directory Open Access Journal
issn 2831-0896
2831-090X
language English
last_indexed 2024-04-24T23:39:15Z
publishDate 2022-09-01
publisher Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
record_format Article
series Biomolecules & Biomedicine
spelling doaj.art-afc118dcc5fe45fa857f5e09992bb15d2024-03-15T13:31:01ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2022-09-0122510.17305/bjbms.2021.6888Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade gliomaJie Wang0Jie Ren1Jifeng Liu2Linyun Zhang3Qihang Yuan4https://orcid.org/0000-0001-7516-7620Bin Dong5Department of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, ChinaDepartment of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, ChinaDepartment of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, ChinaDepartment of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China Accumulating evidence reveals that ferroptosis and pyroptosis play pivotal roles in tumorigenesis of low-grade glioma (LGG). In this research, we aimed to classify molecular subtypes and further identify and verify a novel multigene signature in LGG on the basis of ferroptosis and pyroptosis-related genes (FPRGs). Raw sequencing data and corresponding clinical data of LGG samples retrieved from the TCGA and CGGA databases were obtained for the training and validation datasets. Non-negative matrix factorization (NMF) clustering defined by FPRGs associated with prognosis was performed to classify molecular subtypes of LGG patients. LASSO-SVM-Random Forest analysis was carried out to develop an FPRG signature to predict the survival and benefit of immunotherapy of LGG patients. NMF clustering defined by FPRGs with prognostic values acted to categorize LGG patients into two molecular subtypes with different prognosis, clinical traits and immune microenvironments. A six-FPRG prognostic signature was constructed, accompanied by the optimal p-value. The AUC values of our signature exhibited great prognostic performances. Our signature was superior to other four well-recognized signatures in predicting the survival probability of LGG patients. Immune characteristics, tumor mutation profile, tumor stemness indices, MGMT methylation and immunotherapy response biomarkers showed significant differences between high- and low-risk populations. Finally, a nomogram was created for quantitative prediction of the survival probability of LGG patients, with the AUC values of the nomogram being 0.916, 0.888 and 0.836 for 1-, 3- and 5-year survival, sequentially. Overall, the FPRG signature may function as an effective indicator for the prognosis prediction and immunotherapy response of LGG patients. https://www.bjbms.org/ojs/index.php/bjbms/article/view/6888Ferroptosispyroptosisprognostic signatureimmunotherapylow-grade glioma
spellingShingle Jie Wang
Jie Ren
Jifeng Liu
Linyun Zhang
Qihang Yuan
Bin Dong
Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade glioma
Biomolecules & Biomedicine
Ferroptosis
pyroptosis
prognostic signature
immunotherapy
low-grade glioma
title Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade glioma
title_full Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade glioma
title_fullStr Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade glioma
title_full_unstemmed Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade glioma
title_short Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade glioma
title_sort identification and verification of the ferroptosis and pyroptosis associated prognostic signature for low grade glioma
topic Ferroptosis
pyroptosis
prognostic signature
immunotherapy
low-grade glioma
url https://www.bjbms.org/ojs/index.php/bjbms/article/view/6888
work_keys_str_mv AT jiewang identificationandverificationoftheferroptosisandpyroptosisassociatedprognosticsignatureforlowgradeglioma
AT jieren identificationandverificationoftheferroptosisandpyroptosisassociatedprognosticsignatureforlowgradeglioma
AT jifengliu identificationandverificationoftheferroptosisandpyroptosisassociatedprognosticsignatureforlowgradeglioma
AT linyunzhang identificationandverificationoftheferroptosisandpyroptosisassociatedprognosticsignatureforlowgradeglioma
AT qihangyuan identificationandverificationoftheferroptosisandpyroptosisassociatedprognosticsignatureforlowgradeglioma
AT bindong identificationandverificationoftheferroptosisandpyroptosisassociatedprognosticsignatureforlowgradeglioma