MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis

MAX dimerization protein 3 (MXD3), a transcriptional regulator of the MXD3 superfamily, is a part of the MYC–MAX–MXD network. However, its role in tumors has been reported in several cancers, such as B-cell acute lymphoblastic leukemia, medulloblastoma, neuroblastoma, and glioblastoma. Based on TCGA...

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Autores principales:	Xiaoyu Zhang, Xiaoqin He, Yue Li, Yangtao Xu, Wenliang Chen, Xin Liu, Xinyao Hu, Lin Xiong, Ximing Xu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	MXD3 cancer prognosis methylation immune immune infiltrating cell Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/03a918ac26324d8abc5c93749ca89d8d
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spelling	oai:doaj.org-article:03a918ac26324d8abc5c93749ca89d8d2021-11-11T07:53:40ZMXD3 as an Immunological and Prognostic Factor From Pancancer Analysis2296-889X10.3389/fmolb.2021.702206https://doaj.org/article/03a918ac26324d8abc5c93749ca89d8d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.702206/fullhttps://doaj.org/toc/2296-889XMAX dimerization protein 3 (MXD3), a transcriptional regulator of the MXD3 superfamily, is a part of the MYC–MAX–MXD network. However, its role in tumors has been reported in several cancers, such as B-cell acute lymphoblastic leukemia, medulloblastoma, neuroblastoma, and glioblastoma. Based on TCGA and GEO data, our first pancancer study of MXD3 confirmed the high expression of MXD3 in cancer tissues. Our results revealed that patients suffering from cancers with higher MXD3 expression had poor OS, DSS, DFI, and PFI. We further explored the methylation status of the MXD3 gene body and gene promoter in cancer. Patients with a higher MXD3 gene body have better OS, while the prognosis of patients with a high MXD3 promoter is more complex. We also verified the differential expression of three clinical phenotypes of MXD3: age, sex, and tumor stage, in a variety of tumors, suggesting a correlation between MXD3 and clinical characteristics. We explored the negative relationship between MXD3 and TMB and MSI in most types of cancer, indicating the poor prognosis of patients with high MXD3 expression. We further investigated the relationship between MXD3 and immune infiltrating cells and identified the relationship between MXD3 and immune genes, immunosuppressive genes, and antigen-presenting genes. All of the above findings established a solid relationship between MXD3 and the immune environment and immune cells. These results demonstrated that MXD3 might also be a potential immune factor. We also found a higher expression of MXD3 and promoter according to the increasing glioma WHO grade or histologic types. Glioma patients with high MXD3 or MXD3 promoter expression had poor survival. Finally, we used IHC to verify the higher expression of MXD3 in glioma samples compared to normal samples. Our study shows that MXD3, as a poor prognostic factor, plays a significant role in many cancers, especially glioma. Although more clinical evidence for MXD3 as a clinical therapeutic target and an immunotherapy site is needed, MXD3 can play an important guiding role in multiple clinical treatments, including immunotherapy and demethylation therapy.Xiaoyu ZhangXiaoqin HeYue LiYangtao XuWenliang ChenXin LiuXinyao HuLin XiongXiming XuFrontiers Media S.A.articleMXD3cancerprognosismethylationimmuneimmune infiltrating cellBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MXD3 cancer prognosis methylation immune immune infiltrating cell Biology (General) QH301-705.5
spellingShingle	MXD3 cancer prognosis methylation immune immune infiltrating cell Biology (General) QH301-705.5 Xiaoyu Zhang Xiaoqin He Yue Li Yangtao Xu Wenliang Chen Xin Liu Xinyao Hu Lin Xiong Ximing Xu MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis
description	MAX dimerization protein 3 (MXD3), a transcriptional regulator of the MXD3 superfamily, is a part of the MYC–MAX–MXD network. However, its role in tumors has been reported in several cancers, such as B-cell acute lymphoblastic leukemia, medulloblastoma, neuroblastoma, and glioblastoma. Based on TCGA and GEO data, our first pancancer study of MXD3 confirmed the high expression of MXD3 in cancer tissues. Our results revealed that patients suffering from cancers with higher MXD3 expression had poor OS, DSS, DFI, and PFI. We further explored the methylation status of the MXD3 gene body and gene promoter in cancer. Patients with a higher MXD3 gene body have better OS, while the prognosis of patients with a high MXD3 promoter is more complex. We also verified the differential expression of three clinical phenotypes of MXD3: age, sex, and tumor stage, in a variety of tumors, suggesting a correlation between MXD3 and clinical characteristics. We explored the negative relationship between MXD3 and TMB and MSI in most types of cancer, indicating the poor prognosis of patients with high MXD3 expression. We further investigated the relationship between MXD3 and immune infiltrating cells and identified the relationship between MXD3 and immune genes, immunosuppressive genes, and antigen-presenting genes. All of the above findings established a solid relationship between MXD3 and the immune environment and immune cells. These results demonstrated that MXD3 might also be a potential immune factor. We also found a higher expression of MXD3 and promoter according to the increasing glioma WHO grade or histologic types. Glioma patients with high MXD3 or MXD3 promoter expression had poor survival. Finally, we used IHC to verify the higher expression of MXD3 in glioma samples compared to normal samples. Our study shows that MXD3, as a poor prognostic factor, plays a significant role in many cancers, especially glioma. Although more clinical evidence for MXD3 as a clinical therapeutic target and an immunotherapy site is needed, MXD3 can play an important guiding role in multiple clinical treatments, including immunotherapy and demethylation therapy.
format	article
author	Xiaoyu Zhang Xiaoqin He Yue Li Yangtao Xu Wenliang Chen Xin Liu Xinyao Hu Lin Xiong Ximing Xu
author_facet	Xiaoyu Zhang Xiaoqin He Yue Li Yangtao Xu Wenliang Chen Xin Liu Xinyao Hu Lin Xiong Ximing Xu
author_sort	Xiaoyu Zhang
title	MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis
title_short	MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis
title_full	MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis
title_fullStr	MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis
title_full_unstemmed	MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis
title_sort	mxd3 as an immunological and prognostic factor from pancancer analysis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/03a918ac26324d8abc5c93749ca89d8d
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_version_	1718439280345350144

MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis

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