The association of CMTM6 expression with prognosis and PD-L1 expression in triple-negative breast cancer

Immune checkpoint inhibitors play a vital role in triple-negative breast cancer (TNBC) immunotherapy. A recent study showed that chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) has a crucial role in programmed death-ligand 1 (PD-L1) stability. The aim of this study was to investigate the relationship between CMTM6 and PD-L1 in TNBC and the association with clinical characteristics.

A total of 143 patients, including 75 with human epidermal growth factor receptor 2 (HER2)-driven breast cancer and 68 with TNBC, were included in this study. In 83 paired primary breast cancers (PBCs) and metastatic breast cancers (MBC) comprising 45 HER2-driven breast cancers and 38 TNBC, CMTM6 and PD-L1 were detected based on immunohistochemistry (IHC) with FFPE tissues. Another 60 PBCs comprising 30 HER2-driven breast cancers and 30 TNBC in order to detect CMTM6 and PD-L1 mRNA expressions based on real-time polymerase chain reaction (RT-PCR) using frozen tissues. Furthermore, 153 patients comprising 30 TNBC and 123 HER2-driven breast cancer based on The Cancer Genome Atlas (TCGA) database were used to confirm the difference mRNA expression.

The expression of CMTM6 in patients with TNBC was significantly higher than in those with HER2-driven PBC (IHC, P=0.036, mRNA, P=0.036, TCGA dataset, P=0.039). CMTM6 was correlated with PD-L1 based on IHC in triple-negative MBC (P=0.004); the same result was found based on mRNA data in triple- negative PBC (P=0.021). Moreover, a high expression of CMTM6 in TNBC was associated with poor progression-free survival (PFS) (P=0.030, 95% CI: 1.08-4.57, HR =2.22). After multiple Cox regression analysis, CMTM6 in TNBC emerged as an independent risk factor for PFS (P=0.027, 95% CI: 1.11-5.20, HR =2.40). The expression of PD-L1 was negatively correlated with lymph node metastasis (P=0.026) and was not associated with PFS.

The expression of CMTM6 was higher in TNBC than in HER2-driven breast cancer. In TNBC, CMTM6 was correlated with PD-L1 expression, and potentially could be used as an independent risk factor for predicting PFS.