Molecular and immune characteristics for lung adenocarcinoma patients with CMTM6 overexpression

CMTM6 was identified as an important regulator of the PD-L1 protein. The role of CMTM6 in lung adenocarcinoma (LUAD) has so far remained unclear. We aimed at investigating the role of CMTM6 in LUAD at transcriptome and genomic levels and its relationship with tumor-infiltrating immune cells (TIICs).

We downloaded the data sets of LUAD from TCGA. The genomic profiles containing somatic mutations were analyzed and the transcriptome level of CMTM6 was also obtained. Gene set variation analysis (GSVA) was used to predict the pathway change. In addition, we explored the association between CMTM6 and LUAD immune infiltrates by means of CIBERSORT. The association between CMTM6 and PD-L1 mRNA was analyzed using an integrated repository portal for tumor-immune system interactions (TISIDB) and was further validated in 80 LUAD patients. Kaplan-Meier survival curve and the log-rank test was used to analyze the survival significance of CMTM6.

We found that CMTM6 was downregulated in LUAD. Patients with low CMTM6 expression were more likely to be frequent with somatic mutations. Moreover, GSVA analysis exhibited that CMTM6 was associated with immune responses and inflammatory activities. Specifically, a positive correlation between increased CMTM6 expression and immune infiltrating level of Dendritic cells resting, Eosinophils, Macrophages M1, Macrophages M2, Neutrophils, T cells CD4 memory activated and T cells CD4 memory resting was established. The CMTM6 expression was positively correlated with PD-L1 in both mRNA and protein level. Clinically, patients with high expression of CMTM6 tended to have a better survival.

CMTM6 expression likely had an important effect on TIICs composition and prognosis in LUAD patients. The CMTM6 expression was positively correlated with PD-L1 in LUAD. These findings establish CMTM6 as a promising target for immunotherapeutic prospects.