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.