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

Abstract

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.

Genetic alterations in juvenile cervical clear cell adenocarcinoma unrelated to human papillomavirus

“…In humans, they are encoded by nine genes, CKLF and CMTM1-8. CMTM5, located at 14q11.2, is a polygenic locus associated with a variety of tumors ( 16 , 17 ). Frequent loss of heterozygosity at 14q11.2 in nasopharyngeal carcinoma (NPC) suggests the presence of a functional tumor suppressor gene (TSG) in this region.…”

“…Frequent loss of heterozygosity at 14q11.2 in nasopharyngeal carcinoma (NPC) suggests the presence of a functional tumor suppressor gene (TSG) in this region. Another study confirmed that ~40% of downregulated genes were located at 1p and 14q in anaplastic meningiomas, whereas the 14q11.2 gene NDRG2 was consistently downregulated in grade III meningiomas (17). CMTM5 has at least six RNA spliced forms (CMTM5-v1-v6).…”

Machine Learning-Based Integration Develops a Pyroptosis-Related lncRNA Model to Enhance the Predicted Value of Low-Grade Glioma Patients

“…Individuals between the ages of 20 and 40 are more likely to develop low-grade gliomas (LGGs, WHO category II and III gliomas) [ 5 ]. While LGGs are malignant and have a high mortality rate, their effect on society, families, and people is extraordinarily stressful, although LGG patients have a better prognosis compared to other CNS malignancies [ 6 – 8 ]. Treatment such as surgery, radiation, and chemotherapy have advanced in recent decades, and LGG patients' survival rate is very variable.…”