CMTM6 is positively correlated with PD-L1 expression and immune cells infiltration in lung squamous carcinoma

Int Immunopharmacol. 2020 Nov:88:106864. doi: 10.1016/j.intimp.2020.106864. Epub 2020 Aug 28.

Abstract

Background: The aim of this study was to clarify the association between CMTM6 and PD-L1 expression as well as microenvironment in lung squamous carcinoma (LUSC).

Material and methods: Using Spearman's correlation and Tumor Immune Estimation Resource (TIMER), we analyzed the relationship between CMTM6 and PD-L1 mRNA in LUSC. Immunohistochemistry (IHC) assay was applied to validate the correlation between CMTM6 and PD-L1 protein level in 80 LUSC samples originated from Shandong Provincial Hospital. Then, using The Cancer Genome Atlas (TCGA) database and fisher test, we analyzed the differential mutation genes in high and low CMTM6 expression group. TISIDB was used to explore the distribution of CMTM6 across immune- and molecular-subtypes. TCGA database and Gene Set variation analysis (GSVA) were used to analyze the relationship between CMTM6 and immune genes, immune related pathways.

Result: Positive correlation between CMTM6 and PD-L1 in mRNA and protein level was found in LUSC patients. More gene mutations were found in CMTM6 high expression group compared with low expression group. Meanwhile, we also found the correlation between CMTM6 expression and molecular subtypes, immune genes, immune related pathways. Furthermore, our result revealed that B cells memory, T cells memory testing, T cells folicular helper, macrophages M0, macrophages M1 and neutrophils varied significantly between patients with CMTM6 high and low expression group. Finally, we found that CMTM6 expression was positively related to CD8 + T cell, macrophage, neutrophil and dendtritic cell (all, P < 0.05) and negatively related to CD4 + T cell (P = 0.018).

Conclusion: CMTM6 is positively associated with PD-L1 expression and correlates with infiltration of immune cells in microenvironment of lung squamous carcinoma.

Keywords: CMTM6; Immune cells infiltration; LUSC; PD-L1.

MeSH terms

  • Aged
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Databases, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • MARVEL Domain-Containing Proteins / genetics
  • MARVEL Domain-Containing Proteins / immunology*
  • Male
  • Middle Aged
  • Mutation
  • Myelin Proteins / genetics
  • Myelin Proteins / immunology*
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • CMTM6 protein, human
  • MARVEL Domain-Containing Proteins
  • Myelin Proteins