The PARPscore system using poly (ADP-ribose) polymerase (PARP) family features and tumor immune microenvironment in glioma

Abstract The immune response plays a pivotal role in tumor progression and therapy. However, the influence of protein PAR polymerases (PARPs) modifications on cell infiltration within the tumor microenvironment (TME) remains insufficiently understood. In this study, the Clinical and RNA sequencing d...

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Main Authors: Cheng Zhang, Juan Feng, Xia Zhou, Jie Zhang, Chuming Tao, Hongwei Zhou
Format: Article
Language:English
Published: Springer 2024-12-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-024-01734-2
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author Cheng Zhang
Juan Feng
Xia Zhou
Jie Zhang
Chuming Tao
Hongwei Zhou
author_facet Cheng Zhang
Juan Feng
Xia Zhou
Jie Zhang
Chuming Tao
Hongwei Zhou
author_sort Cheng Zhang
collection DOAJ
description Abstract The immune response plays a pivotal role in tumor progression and therapy. However, the influence of protein PAR polymerases (PARPs) modifications on cell infiltration within the tumor microenvironment (TME) remains insufficiently understood. In this study, the Clinical and RNA sequencing data we performed a comprehensive analysis of PARPs modification patterns, exploring their associations with TME cell infiltration were acquired from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database. To quantify PARPs modification in individual tumors, we developed a novel metric, the PARPscore, derived using principal component analysis. Our findings revealed three distinct PARPs modification patterns, each correlated with unique TME infiltration characteristics and tumor immunophenotypes. These patterns demonstrated predictive value for various clinical parameters, including inflammation stage, tumor subtypes, TME matrix activity, genetic variations, and patient prognosis. Notably, the high PARPscore subtype exhibited features of stromal activation and reduced immune infiltration, indicative of a non-inflamed, immune-excluded TME phenotype, and was associated with poorer survival outcomes. Conversely, lower PARPscore subtypes corresponded to substantial therapeutic benefits and improved outcomes in two independent immunotherapy cohorts. This study underscores the critical role of PARPs modification in shaping the diverse and dynamic TME. By delineating tumor-specific PARPs modification patterns, we provide valuable insights into TME complexity and its implications for immunotherapy.
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spelling doaj-art-a428cbac604a4071a1a2bae7e61317422025-08-20T02:43:33ZengSpringerDiscover Oncology2730-60112024-12-0115111510.1007/s12672-024-01734-2The PARPscore system using poly (ADP-ribose) polymerase (PARP) family features and tumor immune microenvironment in gliomaCheng Zhang0Juan Feng1Xia Zhou2Jie Zhang3Chuming Tao4Hongwei Zhou5Department of Neurosurgery, Zigong Third People’s HospitalOperating Room, Zigong Third People’s HospitalDepartment of Neurology, Fushun People’s HospitalDepartment of Science and Education, Zigong Third People’s HospitalDepartment of Neurosurgery, Zigong Third People’s HospitalDepartment of Cerebrovascular Disease, Suining First People’s HospitalAbstract The immune response plays a pivotal role in tumor progression and therapy. However, the influence of protein PAR polymerases (PARPs) modifications on cell infiltration within the tumor microenvironment (TME) remains insufficiently understood. In this study, the Clinical and RNA sequencing data we performed a comprehensive analysis of PARPs modification patterns, exploring their associations with TME cell infiltration were acquired from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database. To quantify PARPs modification in individual tumors, we developed a novel metric, the PARPscore, derived using principal component analysis. Our findings revealed three distinct PARPs modification patterns, each correlated with unique TME infiltration characteristics and tumor immunophenotypes. These patterns demonstrated predictive value for various clinical parameters, including inflammation stage, tumor subtypes, TME matrix activity, genetic variations, and patient prognosis. Notably, the high PARPscore subtype exhibited features of stromal activation and reduced immune infiltration, indicative of a non-inflamed, immune-excluded TME phenotype, and was associated with poorer survival outcomes. Conversely, lower PARPscore subtypes corresponded to substantial therapeutic benefits and improved outcomes in two independent immunotherapy cohorts. This study underscores the critical role of PARPs modification in shaping the diverse and dynamic TME. By delineating tumor-specific PARPs modification patterns, we provide valuable insights into TME complexity and its implications for immunotherapy.https://doi.org/10.1007/s12672-024-01734-2PARPsTumor microenvironmentGliomaImmunotherapyMutation burden
spellingShingle Cheng Zhang
Juan Feng
Xia Zhou
Jie Zhang
Chuming Tao
Hongwei Zhou
The PARPscore system using poly (ADP-ribose) polymerase (PARP) family features and tumor immune microenvironment in glioma
Discover Oncology
PARPs
Tumor microenvironment
Glioma
Immunotherapy
Mutation burden
title The PARPscore system using poly (ADP-ribose) polymerase (PARP) family features and tumor immune microenvironment in glioma
title_full The PARPscore system using poly (ADP-ribose) polymerase (PARP) family features and tumor immune microenvironment in glioma
title_fullStr The PARPscore system using poly (ADP-ribose) polymerase (PARP) family features and tumor immune microenvironment in glioma
title_full_unstemmed The PARPscore system using poly (ADP-ribose) polymerase (PARP) family features and tumor immune microenvironment in glioma
title_short The PARPscore system using poly (ADP-ribose) polymerase (PARP) family features and tumor immune microenvironment in glioma
title_sort parpscore system using poly adp ribose polymerase parp family features and tumor immune microenvironment in glioma
topic PARPs
Tumor microenvironment
Glioma
Immunotherapy
Mutation burden
url https://doi.org/10.1007/s12672-024-01734-2
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