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...
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Elsevier
2024-03-01
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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. |
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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 |
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