The newly identified immune checkpoint inhibitor CMTM6 (CKLF-like MARVEL transmembrane domain containing 6) is reported as a critical regulator of programmed death ligand (PD-L1) expression by modulating stability through ubiquitination and modulate T cell expression in several tumors. However, the role of CMTM6 has so far remained unclear in esophageal cancer, especially in esophageal squamous cell carcinoma (ESCCs). The aim of this study was to investigate the expression of CMTM6 and PD-L1 and to confirm their predictive roles in ESCC clinical prognosis.
We collected 137 ESCCs patients' pretreatment biopsies from multiple centers in China. CMTM6 and PD-L1 immunohistochemical expressions were evaluated. The correlation between CMTM6 and PD-L1 expression was also determined based on immunohistochemistry and RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) database. The prognostic value (overall survival (OS) and disease-free survival (DFS)) of CMTM6 and PD-L1 were also evaluated.
CMTM6 expression was detected in approximately 70% of ESCCs tumor tissues, and CMTM6 was highly expressed in ESCCs tumor tissues compared to adjacent normal tissues. In addition, PD-L1 expression is always found in CMTM6 positive cases. CMTM6 expression was positively correlated with PD-L1 expression in immunohistochemical data (P<0.05). A positive correlation was also identified in the mRNA expression data (P<0.05). CMTM6 and PD-L1 expression were associated with cancer metastases, but not with patients’ age and gender. In univariate survival analysis found that positive CMTM6 and PD-L1 expression were correlated with poor OS (P<0.05) and inferior DFS (P<0.05). In multivariate survival analysis found that high CMTM6 and PD-L1 co-expression was significantly associated with poor OS (P<0.05) and inferior DFS (P<0.05).
CMTM6 expression is positively associated with PD-L1 expression. High CMTM6 and PD-L1 co-expression correlated with metastasis and predict the poor OS and inferior DFS. Thus, CMTM6 and PD-L1 co-expression can be a promising predictor useful for predicting ESCCs prognosis.
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All authors have declared no conflicts of interest.