背景:乳腺癌是全球最常见的癌症,在所有癌症中死亡率第五高,转移风险高。然而,乳腺癌临床结局分层的潜在生物标志物和分子机制仍有待研究.因此,我们旨在为乳腺癌患者寻找一种新的预后生物标志物和治疗靶点.
方法:使用无监督层次聚类对具有临床病理和生存信息的乳腺癌公共数据集中的共185个糖基因进行全面的转录组学研究。使用Limma软件包发现了用于亚型分类的基于糖基因的签名,GSVA鉴定了与四个已知分子特征的相关性。进行了实验验证,并通过定量RT-PCR表征了B3GNT7的生物学功能,westernblot,transwell分析,和乳腺癌细胞中的凝集素免疫荧光染色。
结果:在乳腺癌的分类中鉴定出23-糖基因标记。在23个糖基因中,在乳腺癌患者中,B3GNTs与ER-/Her2-亚型呈显著正相关(n=2655)。基于公共数据集,过表达的B3GNT7与乳腺癌患者的不良预后相关。B3GNT7耗竭抑制细胞增殖,迁移,和入侵,MDA-MB-231和HCC1937乳腺癌细胞中的整体岩藻糖基化降低。
结论:此处,我们发现了乳腺癌患者糖基因类型分类的独特23个基因特征.在这些基因中,B3GNT7被证明是乳腺癌不利结果和治疗靶标的潜在生物标志物。
BACKGROUND: Breast cancer is the most common cancer worldwide, with the fifth highest mortality rate among all cancers and high risk of metastasis. However, potential biomarkers and molecular mechanisms underlying the stratification of breast cancer in terms of clinical outcomes remain to be investigated. Therefore, we aimed to find a novel prognostic biomarker and therapeutic target for breast cancer patients.
METHODS: Unsupervised hierarchical clustering was used to perform comprehensive transcriptomic study of total 185 glycogenes in public datasets of breast cancer with clinicopathological and survival information. A glycogene-based signature for subtype classification was discovered using Limma packages, and relevance to four known molecular features was identified by GSVA. Experimental verification was performed and biological functions of
B3GNT7 were characterized by quantitative RT-PCR, western blot, transwell assays, and lectin immunofluorescence staining in breast cancer cells.
RESULTS: A 23-glycogene signature was identified for the classification of breast cancer. Among the 23 glycogenes, B3GNTs showed significantly positive associations with ER-/Her2- subtype in breast cancer patients (n = 2655). Overexpressed
B3GNT7 were correlated with poor prognosis in breast cancer patients based on public datasets.
B3GNT7 depletion inhibited cell proliferation, migration, and invasion, and decreased global fucosylation in MDA-MB-231 and HCC1937 breast cancer cells.
CONCLUSIONS: Herein, we discovered a unique 23-gene signature for breast cancer patient glycogene-type classification. Among these genes,
B3GNT7 was shown to be a potential biomarker for unfavorable outcomes and therapeutic target of breast cancer.