Comprehensive analysis of CMTM family and immune infiltration in esophageal carcinoma

Esophageal carcinoma (ESCA) is one of the most common malignant diseases and contributes to the annual burden of death worldwide. A better understanding of the underlying molecular changes is urgently required to identify early diagnostic biomarkers and effective therapeutics. The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTMs) is reported to be entangled in many human cancers. However, the role of CMTMs in ESCA remains unclear.

The differential expressions of CMTMs between ESCA and normal tissues were analyzed using TCGA database. The relationships between CMTMs and immune infiltration in the tumor microenvironment (TME) were also evaluated to explore their underlying values in the diagnosis and prognosis of ESCA.

The results showed that ESCA showed significantly higher expressions of CMTM1,3,6,7 and lower expressions of CMTM4,5 than normal tissue (P < 0.05). Meanwhile, CMTM3,4,8 expressions were correlated with the tumor stage of ECSA patients. The analysis on immune infiltrations (CD8 + T, Tregs, NK and macrophages) showed that M2 macrophages was dominant in TME, with significantly higher levels than the other cells (F = 326.93, P < 0.001). The higher abundance of M2 macrophages and Tregs significantly shortened the survival time of patients with ESCA (P = 0.01). Interestingly, the expression levels of CMTM1,3,5,7 were comparable to the abundance of M2 macrophages (CMTM1: r = 0.172168; CMTM3: r = 0.313221; CMTM5: r = 0.130669; CMTM7: r = 0.119922; P < 0.05). CMTM2,4,5,7,8 positively correlated with Tregs (P < 0.05). Moreover, we found positive associations between the expression of CMTMs and the signatures of M2 macrophages (MS4A4A, VSIG4 and CD163).

There were differential expressions of CMTMs between ESCA and normal tissues. Furthermore, the expression of CMTMs was positively correlated with M2 macrophages, indicating a possibility that CMTMs may become a new immunotherapy target for ESCA.