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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8505737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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