Expression of CMTM6 and PD-L1 in breast cancer and normal breast tissue

Figure 1 shows that the expression of CMTM6 and PD-L1 is higher in breast cancer tissue (Fig. 1B and 1D) compared to normal breast tissue (Fig. 1A and 1 C). Table 1 presents the positive rates of CMTM6 and PD-L1 in breast cancer tissue (64.7%, 10.0%) and normal breast tissue (31.4% and 4.0%). Table 2 reveals a significant positive correlation between the expressions of CMTM6 and PD-L1 in breast cancer tissues (p < 0.001).

Fig. 1

CMTM6 and PD-L1 expression in normal and breast cancer tissue. A and C Expression of CMTM6 and PD-L1 in normal breast tissue. B and D Expression of CMTM6 and PD-L1 in breast cancer. Magnification, × 200. CMTM6, chemokine-like factor-like MARVEL transmembrane domain-containing family member 6; PD-L1, programmed death 1 ligand 1

Table 1 CMTM6 and PD-L1 expression in Normal tissue and breast cancerTable 2 Correlation analysis of CMTM6 and PD-L1 in breast cancerRelationship between the expression of CMTM6 and PD-L1 and the pathological characteristics and prognosis of breast cancer

As shown in Table 3, CMTM6 and PD-L1 expression was associated with lymph node metastasis, TNM stage, vascular infiltration, and HER2-positive breast cancer (P < 0.05). Conversely, CMTM6 expression was positively associated with estrogen receptor (ER)-positive breast cancer and distant metastasis (P < 0.05; Table 3). Kaplan–Meier analysis demonstrated a positive association between high CMTM6 and PD-L1 expression and poor prognosis in patients (Fig. 2A and B; P < 0.05). Univariate analysis revealed that high CMTM6 expression was positively related to lymph node metastasis and the poor prognosis of patients with breast cancer (Table 4; P < 0.05), whereas high PD-L1 expression was positively related to high histological grade and the poor prognosis of patients (Table 4; P < 0.05). Cox multivariate analysis suggested that lymph node metastasis and histological grading are risk factors affecting patient survival time (Table 5; P < 0.05).

Table 3 Relationship between expression of CMTM6 and PD-L1 and Clinicopathological features of breast cancerFig. 2

The relationship between the expression of CMTM6 and PD-L1 and the prognosis of breast cancer patients. Kaplan–Meier analysis shown that high expression of CMTM6 (A) and PD-L1 (B) was negatively correlated with poor prognosis in patients. According to KM plotter database, a higher CMTM6 expression was positively related with overall (C) and relapse-free survival rate of patients (D). A higher PD-L1 expression was positively correlated with overall (E) and relapse-free survival rate of patients (F)

Table 4 Univariate analysis of prognostic risk factors in the patients with breast cancerTable 5 Multivariate analysis of clinicopathological variables for the survival of the patients with breast cancerBioinformatics features of CMTM6 and PD-L1 in breast cancer

According to the KM plotter database, the expression of CMTM6 mRNA was positively correlated with the overall survival rate in ER +, PR-, HER2-, Luminal A, LN +, grade 2/3, and Basal-like 2 subtypes (Fig. 2C and Table 6, p < 0.05). The timer database revealed a close association between CMTM6 and PD-L1 with eight immune cells in breast cancer, demonstrating a positive correlation in their expressions. Similarly, CMTM6 mRNA expression was positively associated with relapse-free survival rate (Fig. 2D), even withER status array ±, PR-, HER2 +, Luminal A, and grade 2 (Table 6; P < 0.05). Furthermore, CMTM6 mRNA expression was found to be positively correlated with the overall survival rate in breast cancer patients (Fig. 2E, p < 0.05). Conversely, patients with ER status IHC-, ER status array-, PR-, HER2 +, Basal, LN +, grade 3, and Basal-like 1 cancer who expressed PD-L1 had a shorter relapse-free survival time compared with those with low PD-L1 expression (Table 7, p < 0.05). High PD-L1 expression showed a positive correlation with the relapse-free survival rate in all cancer patients (Fig. 2F, p < 0.05), even when stratified by ER status array, HER2 status array, and Subtype StGallen(Table 7, p < 0.05), including patients with PR-, LN-, grade 3, Basal-like 1 and 2, mesenchymal, and luminal androgen receptor subtypes.

Table 6 The prognostic significance of CMTM6 mRNA in breast cancerTable 7 The prognostic significance of PD-L1 mRNA in breast cancer

The timer database indicated a close relationship between CMTM6 and PD-L1 with eight immune cells, namely B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells (Fig. 3A–D, p < 0.05). Their expressions were positively correlated in breast invasive carcinoma (Fig. 4A, p < 0.05), breast invasive carcinoma-basal (Fig. 4B, p < 0.05), and breast invasive carcinoma-luminal (Fig. 4C, p < 0.05), except for breast invasive carcinoma-Her2 (Fig. 4D, p > 0.05).

Fig. 3

Correlation of CMTM6 and PD-L1 expression levels with immune cells. A In the Tumor Immune Estimation Resource database, a positive correlation between CMTM6 expression and B cell, CD8 + T cell, CD4 + T cell, B a positive correlation between CMTM6 expression andmacrophage, neutrophil and dendritic cell. C Correlation of PD-L1 expression levels with B cell, CD8 + T cell, CD4 + T cell, D a positive correlation between PD-L1 expression macrophage, neutrophil and dendritic cell. CMTM6, chemokine-like factor-like MARVEL transmembrane domain-containing family member 6; PD-L1, programmed death 1 ligand 1; TPM, transcripts per million

Fig. 4

The correlation between the expression of CMTM6 and PD-L1 in triple-negative breast cancer. Brest invasive carcinoma (A), brest invasive carcinoma-basal (B), brest invasive carcinoma-Luminal (C), and brest invasive carcinoma-Her2 (D)