Huo Qin, Li Zhenwei, Chen Siqi, Wang Juan, Li Jiaying, Xie Ni
Biobank, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University , Shenzhen, 518035, China.
Department of Clinical Medicine , University of South China , Hengyang , 421001 , China.
Cancer Cell Int. 2021 May 21;21(1):272. doi: 10.1186/s12935-021-01955-3.
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 this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer.
The 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.
The 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.
In 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.
血管性血友病因子C和表皮生长因子结构域(VWCE)是一个调节细胞黏附、迁移和相互作用的重要基因。然而,VWCE表达与乳腺癌免疫浸润之间的相关性仍不清楚。在本研究中,我们调查了VWCE表达与乳腺癌免疫浸润水平之间的相关性。
通过肿瘤免疫评估资源(TIMER)和DriverDB数据库分析VWCE的表达。此外,通过STRING和Enrichr网络服务器研究与VWCE共表达的基因以及基因本体(GO)富集分析。同时,我们通过GSCALite进行单核苷酸变异(SNV)、拷贝数变异(CNV)和通路活性分析。随后,通过TIMER和TISIDB数据库分析VWCE表达与肿瘤免疫的关系,并使用定量实时聚合酶链反应(RT-PCR)、蛋白质免疫印迹法和免疫组织化学进一步验证结果。
结果显示,乳腺癌组织中VWCE mRNA的表达明显低于正常组织。我们发现VWCE的表达水平与乳腺癌患者的亚型、雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)状态相关,但在年龄和淋巴结状态方面VWCE的表达没有显著差异。进一步分析表明,VWCE与多种致癌通路的激活或抑制相关。此外,VWCE表达与STAT1(Th1标志物,r = -0.12,p = 6e-05)的表达呈负相关,但与MS4A4A的表达呈正相关(r = 0.28,p = 0)。这些结果表明,VWCE的表达与乳腺癌中Th1和M2巨噬细胞的免疫浸润水平相关。
在我们的研究中,VWCE表达与较好的预后相关,且与乳腺癌的免疫浸润有关。这些发现表明,VWCE是一种潜在的预后生物标志物,与肿瘤免疫细胞浸润相关,可能是乳腺癌中有前景的治疗靶点。