Abstract
PurposeVon 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 this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer.MethodsThe expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. 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 through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry.ResultsThe results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. 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 breast cancer patients, but there was no significant difference in the expression of VWCE 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 was 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 correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer.ConclusionsIn our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.
Highlights
Breast cancer is the most common type of cancer and second death-leading cancer type in women [1,2,3]
We found that there was significant difference between the expression of Von Willebrand Factor C and EGF Domains (VWCE) and subtypes (HER2-E > basallike, p < 0.0001; luminal A < basal-like, p < 0.0001; luminal A < human epidermal growth factor receptor-2 (HER2)-E, p < 0.0001; luminal B < HER2-E, p < 0.0001) (Fig. 3f ). These results suggest that VWCE expression may serve as a potential diagnostic indicator in breast cancer
Correlation analysis between VWCE expression and immune marker sets To detect the relationship between VWCE expression and various immune infiltrating cells, we focused on the correlation between VWCE expression and immune marker sets of various immune cells in Breast invasive carcinoma (BRCA) using the tumor immune estimation resource (TIMER) database
Summary
Breast cancer is the most common type of cancer and second death-leading cancer type in women [1,2,3]. As a newly identified gene, VWCE has been reported to be highly expressed in pancreatic cancer tissues. VWCE promotes the G1/S phase transformation of gastric cancer cells and increases cell adhesion and invasion ability. The function of VWCE is closely related to signal transduction, which regulates cell adhesion, migration, and interaction [15], and promotes cancer development and progression [16]. These results propose that VWCE may be a novel proto-oncogene. The interaction between VWCE expression and immune infiltration in breast cancer remains an unsolved problem
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