CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing Pathways

Lower-grade glioma (LGG) is one of the most common primary tumor types in adults. The chemokine-like factor (CKLF)-like Marvel transmembrane domain-containing (CMTM) family is widely expressed in the immune system and can modulate tumor progression. However, the role of the CMTM family in LGG remain...

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Main Authors: Zeyu Wang, Jingwei Zhang, Hao Zhang, Ziyu Dai, Xisong Liang, Shuwang Li, Renjun Peng, Xun Zhang, Fangkun Liu, Zhixiong Liu, Kui Yang, Quan Cheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.740822/full
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author Zeyu Wang
Zeyu Wang
Jingwei Zhang
Jingwei Zhang
Hao Zhang
Ziyu Dai
Xisong Liang
Shuwang Li
Renjun Peng
Xun Zhang
Fangkun Liu
Zhixiong Liu
Zhixiong Liu
Zhixiong Liu
Kui Yang
Quan Cheng
Quan Cheng
Quan Cheng
author_facet Zeyu Wang
Zeyu Wang
Jingwei Zhang
Jingwei Zhang
Hao Zhang
Ziyu Dai
Xisong Liang
Shuwang Li
Renjun Peng
Xun Zhang
Fangkun Liu
Zhixiong Liu
Zhixiong Liu
Zhixiong Liu
Kui Yang
Quan Cheng
Quan Cheng
Quan Cheng
author_sort Zeyu Wang
collection DOAJ
description Lower-grade glioma (LGG) is one of the most common primary tumor types in adults. The chemokine-like factor (CKLF)-like Marvel transmembrane domain-containing (CMTM) family is widely expressed in the immune system and can modulate tumor progression. However, the role of the CMTM family in LGG remains unknown. A total of 508 LGG patients from The Cancer Genome Atlas (TCGA) database were used as a training cohort, and 155 LGG patients from the Chinese Glioma Genome Atlas (CGGA) array database, 142 LGG patients from the CGGA RNA-sequencing database, and 168 LGG patients from the GSE108474 database were used as the validation cohorts. Patients were subdivided into two groups using consensus clustering. The ENET algorithm was applied to build a scoring model based on the cluster model. Finally, ESTIMATE, CIBERSORT, and xCell algorithms were performed to define the tumor immune landscape. The expression levels of the CMTM family genes were associated with glioma grades and isocitrate dehydrogenase (IDH) status. Patients in cluster 2 and the high-risk score group exhibited a poor prognosis and were enriched with higher grade, wild-type IDH (IDH-WT), 1p19q non-codeletion, MGMT promoter unmethylation, and IDH-WT subtype. Patients in cluster 1 and low-risk score group were associated with high tumor purity and reduced immune cell infiltration. Enrichment pathways analysis indicated that several essential pathways involved in tumor progression were associated with the expression of CMTM family genes. Importantly, PD-1, PD-L1, and PD-L2 expression levels were increased in cluster 2 and high-risk groups. Therefore, the CMTM family contributes to LGG progression through modulating tumor immune landscape.
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spelling doaj.art-8107e0911fa44e5abd7a2666f716d4672022-12-22T00:06:14ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-02-011010.3389/fcell.2022.740822740822CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing PathwaysZeyu Wang0Zeyu Wang1Jingwei Zhang2Jingwei Zhang3Hao Zhang4Ziyu Dai5Xisong Liang6Shuwang Li7Renjun Peng8Xun Zhang9Fangkun Liu10Zhixiong Liu11Zhixiong Liu12Zhixiong Liu13Kui Yang14Quan Cheng15Quan Cheng16Quan Cheng17Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaClinical Diagnosis and Therapy Center for Glioma of Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaClinical Diagnosis and Therapy Center for Glioma of Xiangya Hospital, Central South University, Changsha, ChinaLower-grade glioma (LGG) is one of the most common primary tumor types in adults. The chemokine-like factor (CKLF)-like Marvel transmembrane domain-containing (CMTM) family is widely expressed in the immune system and can modulate tumor progression. However, the role of the CMTM family in LGG remains unknown. A total of 508 LGG patients from The Cancer Genome Atlas (TCGA) database were used as a training cohort, and 155 LGG patients from the Chinese Glioma Genome Atlas (CGGA) array database, 142 LGG patients from the CGGA RNA-sequencing database, and 168 LGG patients from the GSE108474 database were used as the validation cohorts. Patients were subdivided into two groups using consensus clustering. The ENET algorithm was applied to build a scoring model based on the cluster model. Finally, ESTIMATE, CIBERSORT, and xCell algorithms were performed to define the tumor immune landscape. The expression levels of the CMTM family genes were associated with glioma grades and isocitrate dehydrogenase (IDH) status. Patients in cluster 2 and the high-risk score group exhibited a poor prognosis and were enriched with higher grade, wild-type IDH (IDH-WT), 1p19q non-codeletion, MGMT promoter unmethylation, and IDH-WT subtype. Patients in cluster 1 and low-risk score group were associated with high tumor purity and reduced immune cell infiltration. Enrichment pathways analysis indicated that several essential pathways involved in tumor progression were associated with the expression of CMTM family genes. Importantly, PD-1, PD-L1, and PD-L2 expression levels were increased in cluster 2 and high-risk groups. Therefore, the CMTM family contributes to LGG progression through modulating tumor immune landscape.https://www.frontiersin.org/articles/10.3389/fcell.2022.740822/fullCMTMlower-grade gliomamicro-environmentimmune infiltrationprognosis
spellingShingle Zeyu Wang
Zeyu Wang
Jingwei Zhang
Jingwei Zhang
Hao Zhang
Ziyu Dai
Xisong Liang
Shuwang Li
Renjun Peng
Xun Zhang
Fangkun Liu
Zhixiong Liu
Zhixiong Liu
Zhixiong Liu
Kui Yang
Quan Cheng
Quan Cheng
Quan Cheng
CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing Pathways
Frontiers in Cell and Developmental Biology
CMTM
lower-grade glioma
micro-environment
immune infiltration
prognosis
title CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing Pathways
title_full CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing Pathways
title_fullStr CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing Pathways
title_full_unstemmed CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing Pathways
title_short CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing Pathways
title_sort cmtm family genes affect prognosis and modulate immunocytes infiltration in grade ii iii glioma patients by influencing the tumor immune landscape and activating associated immunosuppressing pathways
topic CMTM
lower-grade glioma
micro-environment
immune infiltration
prognosis
url https://www.frontiersin.org/articles/10.3389/fcell.2022.740822/full
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