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A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma

Background: Immune checkpoint inhibitors have been successfully used in a variety of tumors, however, the efficacy of immune checkpoint blockade therapy for patients with glioma is limited. In this study, we tried to clarify gene expression signatures related to the prognosis of gliomas and construc...

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Autores principales: Lin, Cha, Chen, Jian, Su, Zhaoying, Liu, Pei, Liu, Zheyu, Zhu, Chenchen, Xu, Dan, Lin, Zhongda, Xu, Pei, Liu, Ganqiang, Liu, Xinjian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505737/
https://www.ncbi.nlm.nih.gov/pubmed/34650975
http://dx.doi.org/10.3389/fcell.2021.723103
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author Lin, Cha
Chen, Jian
Su, Zhaoying
Liu, Pei
Liu, Zheyu
Zhu, Chenchen
Xu, Dan
Lin, Zhongda
Xu, Pei
Liu, Ganqiang
Liu, Xinjian
author_facet Lin, Cha
Chen, Jian
Su, Zhaoying
Liu, Pei
Liu, Zheyu
Zhu, Chenchen
Xu, Dan
Lin, Zhongda
Xu, Pei
Liu, Ganqiang
Liu, Xinjian
author_sort Lin, Cha
collection PubMed
description Background: Immune checkpoint inhibitors have been successfully used in a variety of tumors, however, the efficacy of immune checkpoint blockade therapy for patients with glioma is limited. In this study, we tried to clarify gene expression signatures related to the prognosis of gliomas and construct a signature to predict the survival of patients with gliomas. Methods: Calcium-related differential expressed genes (DEGs) between gliomas and normal brain tissues were comprehensively analyzed in two independent databases. Univariate, multivariate Cox regression analysis and proportional hazards model were used to identify the prognostic of calcium-related risk score signature. The CIBERSORT algorithm and association analysis were carried out to evaluate the relationship between calcium-related signature and characteristic clinical features, tumor-infiltrating immune cell signatures as well as immune checkpoint molecules in glioma. A nomogram model was developed for predicting the overall survival for patients with gliomas. Results: We found the intersection of 415 DEGs between gliomas and normal brain tissues, and identified that an eighteen calcium-related gene panel was significantly enriched in these DEGs. A calcium-related signature derived risk score was developed to divide patients into high- and low-risk groups. Low levels of calcium-related gene expression in high-risk score cases were accompanied with worse outcomes of patients. Calcium-related risk scores were significantly associated with characteristic clinical features, immune infiltrating signatures of tumor microenvironment, and exhausted T cell markers including programmed cell death 1 (PD-1), lymphocyte activating 3 (LAG3), and T cell membrane protein 3 (TIM-3), which contribute to an adverse therapeutic effect of immunotherapy. Calcium-related signature risk score was considered as an independent prognostic parameter to predict the of overall survival of patients with gliomas in nomogram model. Conclusion: Our study demonstrated that calcium signaling pathway is highly associated with immunosuppression of gliomas and overall survival of patients. Targeting the calcium signaling pathway might be a new strategy to reverse the immunosuppressive microenvironment of gliomas and improve the efficacy of glioma immunotherapy.
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spelling pubmed-85057372021-10-13 A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma Lin, Cha Chen, Jian Su, Zhaoying Liu, Pei Liu, Zheyu Zhu, Chenchen Xu, Dan Lin, Zhongda Xu, Pei Liu, Ganqiang Liu, Xinjian Front Cell Dev Biol Cell and Developmental Biology Background: Immune checkpoint inhibitors have been successfully used in a variety of tumors, however, the efficacy of immune checkpoint blockade therapy for patients with glioma is limited. In this study, we tried to clarify gene expression signatures related to the prognosis of gliomas and construct a signature to predict the survival of patients with gliomas. Methods: Calcium-related differential expressed genes (DEGs) between gliomas and normal brain tissues were comprehensively analyzed in two independent databases. Univariate, multivariate Cox regression analysis and proportional hazards model were used to identify the prognostic of calcium-related risk score signature. The CIBERSORT algorithm and association analysis were carried out to evaluate the relationship between calcium-related signature and characteristic clinical features, tumor-infiltrating immune cell signatures as well as immune checkpoint molecules in glioma. A nomogram model was developed for predicting the overall survival for patients with gliomas. Results: We found the intersection of 415 DEGs between gliomas and normal brain tissues, and identified that an eighteen calcium-related gene panel was significantly enriched in these DEGs. A calcium-related signature derived risk score was developed to divide patients into high- and low-risk groups. Low levels of calcium-related gene expression in high-risk score cases were accompanied with worse outcomes of patients. Calcium-related risk scores were significantly associated with characteristic clinical features, immune infiltrating signatures of tumor microenvironment, and exhausted T cell markers including programmed cell death 1 (PD-1), lymphocyte activating 3 (LAG3), and T cell membrane protein 3 (TIM-3), which contribute to an adverse therapeutic effect of immunotherapy. Calcium-related signature risk score was considered as an independent prognostic parameter to predict the of overall survival of patients with gliomas in nomogram model. Conclusion: Our study demonstrated that calcium signaling pathway is highly associated with immunosuppression of gliomas and overall survival of patients. Targeting the calcium signaling pathway might be a new strategy to reverse the immunosuppressive microenvironment of gliomas and improve the efficacy of glioma immunotherapy. Frontiers Media S.A. 2021-09-28 /pmc/articles/PMC8505737/ /pubmed/34650975 http://dx.doi.org/10.3389/fcell.2021.723103 Text en Copyright © 2021 Lin, Chen, Su, Liu, Liu, Zhu, Xu, Lin, Xu, Liu and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Lin, Cha
Chen, Jian
Su, Zhaoying
Liu, Pei
Liu, Zheyu
Zhu, Chenchen
Xu, Dan
Lin, Zhongda
Xu, Pei
Liu, Ganqiang
Liu, Xinjian
A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma
title A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma
title_full A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma
title_fullStr A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma
title_full_unstemmed A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma
title_short A Calcium-Related Immune Signature in Prognosis Prediction of Patients With Glioma
title_sort calcium-related immune signature in prognosis prediction of patients with glioma
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505737/
https://www.ncbi.nlm.nih.gov/pubmed/34650975
http://dx.doi.org/10.3389/fcell.2021.723103
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