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

Yiping Tian; Xiaohui Sun; Guoping Cheng; Enming Ji; Shifeng Yang; Jianguo Feng; Linfeng Zheng

doi:10.21037/atm-20-7616

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

Ann Transl Med. 2021 Jan;9(2):131. doi: 10.21037/atm-20-7616.

Authors

Yiping Tian^{1

2}, Xiaohui Sun³, Guoping Cheng^{1

2}, Enming Ji^{1

2}, Shifeng Yang^{1

2}, Jianguo Feng^{2

4}, Linfeng Zheng^{1

2}

Affiliations

¹ Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
² Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, China.
³ Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China.
⁴ Department of Experimental Research Center, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: CMTM6; PD-L1; immunohistochemistry (IHC); polymerase chain reaction (PCR); prognosis; triple-negative breast cancer (TNBC).