Significant role of PPP3CB in malignant gliomas development, prognosis and potential therapeutic application—a study based on comprehensive bioinformatics, cell experiments and immunohistochemistry analyses

Introduction: Malignant gliomas are the most prevalent and fatal types of primary malignant brain tumors with poor prognosis. Protein phosphatase 3 catalytic subunit beta (PPP3CB) is a pivotal constituent of the Ca2+/calmodulin-dependent serine/threonine protein phosphatases and widely expressed in...

Full description

Bibliographic Details
Main Authors: Bo Li, Ziyi Yang, Lulu Li, Yongxin Wang, Feng Jin, Lu Zhang, Youjing Zhang
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Biochemistry and Biophysics Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S240558082300184X
_version_ 1797317121870397440
author Bo Li
Ziyi Yang
Lulu Li
Yongxin Wang
Feng Jin
Lu Zhang
Youjing Zhang
author_facet Bo Li
Ziyi Yang
Lulu Li
Yongxin Wang
Feng Jin
Lu Zhang
Youjing Zhang
author_sort Bo Li
collection DOAJ
description Introduction: Malignant gliomas are the most prevalent and fatal types of primary malignant brain tumors with poor prognosis. Protein phosphatase 3 catalytic subunit beta (PPP3CB) is a pivotal constituent of the Ca2+/calmodulin-dependent serine/threonine protein phosphatases and widely expressed in brain. We aimed at identifying whether PPP3CB has potential in being a novel biomarker of malignant gliomas, bringing new insights to clinical management and therapy. Methods: Transcriptomes and clinical data of Glioblastoma (GBM) and low-grade glioma (LGG) samples were downloaded from TCGA and CGGA. We first explored the expressional and survival features of tumor tissues. Then, PPP3CB-associated genes were identified and their functional pathways were explored through GSEA analyses. Western blotting was conducted to modify PPP3CB expression. Samples of glioma patients and healthy controls were collected and immunohistochemistry (IHC) staining was performed to detect protein level. Further, we carried out an immune infiltration analysis, explored the correlation between PPP3CB and immune checkpoint genes, as well as to assessed the tumor mutation burden (TMB) and tumor microenvironment score (TMEscore) of PPP3CB. Results: PPP3CB expression in malignant glioma tissues was significantly downregulated and was considered an independent prognostic factor. Several functional pathways were observed through functional pathway analyses. PPP3CB's expression was strongly related to the infiltration of various immune cells and expression of key immune checkpoint genes. PPP3CB expression in high-grade gliomas was significantly lower, affecting glioma cells' proliferation and apoptosis in vitro. Conclusion: PPP3CB was a potential biomarker for the diagnosis and prognosis of malignant gliomas.
first_indexed 2024-03-08T03:30:17Z
format Article
id doaj.art-5d746dd5d4e84488bac3be9fb36ab133
institution Directory Open Access Journal
issn 2405-5808
language English
last_indexed 2024-03-08T03:30:17Z
publishDate 2024-03-01
publisher Elsevier
record_format Article
series Biochemistry and Biophysics Reports
spelling doaj.art-5d746dd5d4e84488bac3be9fb36ab1332024-02-11T05:11:13ZengElsevierBiochemistry and Biophysics Reports2405-58082024-03-0137101603Significant role of PPP3CB in malignant gliomas development, prognosis and potential therapeutic application—a study based on comprehensive bioinformatics, cell experiments and immunohistochemistry analysesBo Li0Ziyi Yang1Lulu Li2Yongxin Wang3Feng Jin4Lu Zhang5Youjing Zhang6Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, Shandong, ChinaKey Laboratory of Cardiovascular Epidemiology, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, ChinaDivision of Surgical Intensive Care Unit, Cardiac Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaThe Affiliated Qingdao Central Hospital of Qingdao University, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, 266042, Shandong, ChinaDepartment of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, Shandong, ChinaKey Laboratory of Cardiovascular Epidemiology, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China; Corresponding author.Introduction: Malignant gliomas are the most prevalent and fatal types of primary malignant brain tumors with poor prognosis. Protein phosphatase 3 catalytic subunit beta (PPP3CB) is a pivotal constituent of the Ca2+/calmodulin-dependent serine/threonine protein phosphatases and widely expressed in brain. We aimed at identifying whether PPP3CB has potential in being a novel biomarker of malignant gliomas, bringing new insights to clinical management and therapy. Methods: Transcriptomes and clinical data of Glioblastoma (GBM) and low-grade glioma (LGG) samples were downloaded from TCGA and CGGA. We first explored the expressional and survival features of tumor tissues. Then, PPP3CB-associated genes were identified and their functional pathways were explored through GSEA analyses. Western blotting was conducted to modify PPP3CB expression. Samples of glioma patients and healthy controls were collected and immunohistochemistry (IHC) staining was performed to detect protein level. Further, we carried out an immune infiltration analysis, explored the correlation between PPP3CB and immune checkpoint genes, as well as to assessed the tumor mutation burden (TMB) and tumor microenvironment score (TMEscore) of PPP3CB. Results: PPP3CB expression in malignant glioma tissues was significantly downregulated and was considered an independent prognostic factor. Several functional pathways were observed through functional pathway analyses. PPP3CB's expression was strongly related to the infiltration of various immune cells and expression of key immune checkpoint genes. PPP3CB expression in high-grade gliomas was significantly lower, affecting glioma cells' proliferation and apoptosis in vitro. Conclusion: PPP3CB was a potential biomarker for the diagnosis and prognosis of malignant gliomas.http://www.sciencedirect.com/science/article/pii/S240558082300184XProtein phosphatase 3 catalytic subunit beta (PPP3CB)Malignant gliomasBioinformatics analysesCell experimentsImmunohistochemistry
spellingShingle Bo Li
Ziyi Yang
Lulu Li
Yongxin Wang
Feng Jin
Lu Zhang
Youjing Zhang
Significant role of PPP3CB in malignant gliomas development, prognosis and potential therapeutic application—a study based on comprehensive bioinformatics, cell experiments and immunohistochemistry analyses
Biochemistry and Biophysics Reports
Protein phosphatase 3 catalytic subunit beta (PPP3CB)
Malignant gliomas
Bioinformatics analyses
Cell experiments
Immunohistochemistry
title Significant role of PPP3CB in malignant gliomas development, prognosis and potential therapeutic application—a study based on comprehensive bioinformatics, cell experiments and immunohistochemistry analyses
title_full Significant role of PPP3CB in malignant gliomas development, prognosis and potential therapeutic application—a study based on comprehensive bioinformatics, cell experiments and immunohistochemistry analyses
title_fullStr Significant role of PPP3CB in malignant gliomas development, prognosis and potential therapeutic application—a study based on comprehensive bioinformatics, cell experiments and immunohistochemistry analyses
title_full_unstemmed Significant role of PPP3CB in malignant gliomas development, prognosis and potential therapeutic application—a study based on comprehensive bioinformatics, cell experiments and immunohistochemistry analyses
title_short Significant role of PPP3CB in malignant gliomas development, prognosis and potential therapeutic application—a study based on comprehensive bioinformatics, cell experiments and immunohistochemistry analyses
title_sort significant role of ppp3cb in malignant gliomas development prognosis and potential therapeutic application a study based on comprehensive bioinformatics cell experiments and immunohistochemistry analyses
topic Protein phosphatase 3 catalytic subunit beta (PPP3CB)
Malignant gliomas
Bioinformatics analyses
Cell experiments
Immunohistochemistry
url http://www.sciencedirect.com/science/article/pii/S240558082300184X
work_keys_str_mv AT boli significantroleofppp3cbinmalignantgliomasdevelopmentprognosisandpotentialtherapeuticapplicationastudybasedoncomprehensivebioinformaticscellexperimentsandimmunohistochemistryanalyses
AT ziyiyang significantroleofppp3cbinmalignantgliomasdevelopmentprognosisandpotentialtherapeuticapplicationastudybasedoncomprehensivebioinformaticscellexperimentsandimmunohistochemistryanalyses
AT lululi significantroleofppp3cbinmalignantgliomasdevelopmentprognosisandpotentialtherapeuticapplicationastudybasedoncomprehensivebioinformaticscellexperimentsandimmunohistochemistryanalyses
AT yongxinwang significantroleofppp3cbinmalignantgliomasdevelopmentprognosisandpotentialtherapeuticapplicationastudybasedoncomprehensivebioinformaticscellexperimentsandimmunohistochemistryanalyses
AT fengjin significantroleofppp3cbinmalignantgliomasdevelopmentprognosisandpotentialtherapeuticapplicationastudybasedoncomprehensivebioinformaticscellexperimentsandimmunohistochemistryanalyses
AT luzhang significantroleofppp3cbinmalignantgliomasdevelopmentprognosisandpotentialtherapeuticapplicationastudybasedoncomprehensivebioinformaticscellexperimentsandimmunohistochemistryanalyses
AT youjingzhang significantroleofppp3cbinmalignantgliomasdevelopmentprognosisandpotentialtherapeuticapplicationastudybasedoncomprehensivebioinformaticscellexperimentsandimmunohistochemistryanalyses