Dong Xingxing, Yang Yalong, Yuan Qianqian, Hou Jinxuan, Wu Gaosong
Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Genet. 2021 Dec 13;12:768140. doi: 10.3389/fgene.2021.768140. eCollection 2021.
Cell migration-inducing hyaluronidase 1 (CEMIP), a Wnt-related protein and also known as KIAA1199, is implicated in the process of metastatic colonization in a variety of malignant tumors, including breast cancer (BC), which is one of the most frequently diagnosed tumors in women worldwide. In this study, multiple public databases, online analytical tools, and bioinformatics approaches were applied to explore the expression levels, regulatory mechanisms, and biological functions of CEMIP in BC. We illustrated that was highly expressed in various kinds of carcinomas, including BC, especially advanced subtypes, and predicted less favorable prognosis (negatively associated with overall survival) in BC patients, which might be an independent prognostic factor. Then, we revealed that the mutation and high expression of might lead to it as an oncogene. We also demonstrated that mutation, DNA hypo-methylation, and the expression changes of three potential upstream transcription factors (, and ) of were likely to cause the hyperexpression of in BC Moreover, our findings suggested that CEMIP might exert its carcinogenic roles in the tumor microenvironment via participation in the extracellular matrix formation, increasing cancer-associated fibroblast (CAF), M2 macrophage, and neutrophil infiltration and decreasing CD8 T cell infiltration. In summary, our study provided more solid evidence for CEMIP as a prognostic and metastatic biomarker and a potential therapeutic target in BC. Of course, these findings also need more confirmations of basic experiments and further clinical trials in the future.
细胞迁移诱导透明质酸酶1(CEMIP)是一种与Wnt相关的蛋白质,也被称为KIAA1199,在包括乳腺癌(BC)在内的多种恶性肿瘤的转移定植过程中发挥作用,乳腺癌是全球女性中最常被诊断出的肿瘤之一。在本研究中,我们应用了多个公共数据库、在线分析工具和生物信息学方法来探索CEMIP在乳腺癌中的表达水平、调控机制和生物学功能。我们发现CEMIP在包括乳腺癌在内的各种癌症中高表达,尤其是在晚期亚型中,并且预测乳腺癌患者的预后较差(与总生存期呈负相关),这可能是一个独立的预后因素。然后,我们揭示了CEMIP的突变和高表达可能导致其成为一种癌基因。我们还证明,CEMIP的突变、DNA低甲基化以及其三个潜在上游转录因子([此处原文缺失具体因子名称])的表达变化可能导致其在乳腺癌中过度表达。此外,我们的研究结果表明,CEMIP可能通过参与细胞外基质形成、增加癌症相关成纤维细胞(CAF)、M2巨噬细胞和中性粒细胞浸润以及减少CD8 T细胞浸润,在肿瘤微环境中发挥致癌作用。总之,我们的研究为CEMIP作为乳腺癌的预后和转移生物标志物以及潜在治疗靶点提供了更确凿的证据。当然,这些发现未来还需要更多基础实验的证实和进一步的临床试验。