AUTHOR=Wang Zeyu , Zhang Jingwei , Zhang Hao , Dai Ziyu , Liang Xisong , Li Shuwang , Peng Renjun , Zhang Xun , Liu Fangkun , Liu Zhixiong , Yang Kui , Cheng Quan 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.740822

DOI=10.3389/fcell.2022.740822

ISSN=2296-634X

ABSTRACT=Low-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 and 142 LGG patients from the CGGA RNA-sequencing database were used as the validation cohorts. Patients were subdivided into two groups using consensus clustering. LASSO algorithm was applied to build a scoring model. Finally, ESTIMATE, CIBERSORT, and xCell algorithms were performed to define the tumor immune landscape. The expression levels of CMTM family genes were associated with glioma grades and isocitrate dehydrogenase (IDH) status. Patients in cluster 1 were associated with high tumor purity and reduced immune cell infiltration. Moreover, cluster 1 had a lower ESTIMATE, immune and stromal score than cluster 2. Patients in the high-risk 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. In addition, patients in cluster 2 were prone to have a high-risk score. 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. In conclusion, the CMTM family could predict the prognosis of grade II/III glioma patients by affecting the tumor immune landscape and activating associated immunosuppressing pathways.