VWCE Serves as a Potential Prognostic Biomarker and is Associated With Immune Infiltrates in Breast Cancer

Abstract Background: Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In the study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer.Methods: VWCE expression was analyzed by the tumor immune estimation resource (TIMER) and DriverDB database. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis by GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB database, and further verified the results using immunohistochemistry. Results: The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissue. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of patients with breast cancer, while no significant expression difference of VWCE mRNA was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression showed negatively correlated with the expression of STAT1 (Th1 marker, r = -0.12, p = 6e-05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was significantly correlates the immune infiltration levels of Th1 and M2 macrophage in breast cancer. Conclusions: The high expression of VWCE indicates a better prognosis and associated with immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.