Molecular and immune characteristics for lung adenocarcinoma patients with CMTM6 overexpression
Molecular and immune characteristics for lung adenocarcinoma patients with CMTM6 overexpression
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DOI：
10.1016/j.intimp.2020.106478
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Wang, Haiyong
中科院分区：
文献类型：
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作者：
Wang, Hui;Gao, Jinping;Wang, Haiyong
背景：CMTM6被认为是PD-L1蛋白的重要调节因子。到目前为止，CMTM6在肺腺癌中的作用尚不清楚。我们旨在从转录组和基因组水平探讨CMTM6在LUAD中的作用及其与肿瘤浸润性免疫细胞(TIICs)的关系。对含有体细胞突变的基因组图谱进行了分析，获得了CMTM6的转录组水平。用基因集变异分析(GSVA)预测通路的改变。此外，我们还通过CiberSort方法探讨了CMTM6与LUAD免疫浸润物之间的关系。使用肿瘤-免疫系统相互作用综合信息库门户(TISIDB)分析CMTM6和PD-L1mRNA之间的关联，并在80例LUAD患者中进一步验证。采用Kaplan-Meier生存曲线和对数列检验分析CMTM6的生存意义。结果：LUAD患者CMTM6基因表达下调。CMTM6低表达的患者更容易发生体细胞突变。GSVA分析表明，CMTM6与免疫反应和炎症活动有关。CMTM6表达增强与树突状细胞静止、嗜酸性粒细胞、巨噬细胞M1、巨噬细胞M2、中性粒细胞、T细胞CD4记忆激活和T细胞CD4记忆静止的免疫浸润水平呈正相关。CMTM6的表达与PD-L1在mRNA和蛋白水平均呈正相关。结论：CMTM6的表达可能对LUAD患者的TIICs构成和预后有重要影响。LUAD中CMTM6的表达与PD-L1呈正相关。这些发现使CMTM6成为免疫治疗前景的一个有前途的靶点。
Background: 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).Methods: 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.Results: 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.Conclusion: 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.