Universidade Federal de Pernambuco, Laboratório de Imunopatologia Keizo Asami, Recife, Pernambuco, Brazil.
Department of Biochemistry, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.
Glycoconj J. 2020 Apr;37(2):263-275. doi: 10.1007/s10719-020-09914-2. Epub 2020 Feb 15.
The complex enzyme network responsible for glycan synthesis suffers significant changes during the first steps of tumor development, leading to the early formation of tumor-associated glycan signatures. Among the glycosylation pathways, changes in fucosylation emerged as one of most important features in cancer. Αlpha-1,3/4-fucosyltransferase (FUT3) has been linked to pro-tumor and anti-tumor pathways depending on the cancer type. The present study aimed to understand the gene and protein expression profiles of FUT3 in three different and independent cohorts composed by invasive breast cancer patients: Local Brazilian population, METABRIC and TCGA. FUT3 transcripts and protein were measured in the Brazilian population by real-time PCR and Western blotting, respectively. Clinical records and FUT3 levels from public METABRIC and TCGA cohorts were accessed through CBioPortal database. FUT3 expression was analyzed in each cohort using the appropriated statistic tools. Survival meta-analysis in triple negative patients was performed using five independent cohorts including GSE41119, GSE47994 and GSE86945, data obtained from GEO repository available at NCBI database, and METABRIC and TCGA. Our analysis showed that high FUT3 levels were consistently associated to reduced invasive breast cancer patients overall survival. This finding is particularly significant in triple negative patients. These results together with the previously knowledge regarding the involvement of FUT3 in pro-tumor and anti-tumor mechanisms led us to purpose a model for FUT3 expression regulation throughout breast cancer establishment and progression.
负责聚糖合成的复杂酶网络在肿瘤发展的早期阶段会发生显著变化，导致肿瘤相关聚糖特征的早期形成。在糖基化途径中，岩藻糖基化的改变被认为是癌症的最重要特征之一。α-1,3/4-岩藻糖基转移酶（FUT3）的活性取决于肿瘤类型，与促肿瘤和抗肿瘤途径有关。本研究旨在了解三种不同且独立的浸润性乳腺癌患者队列中 FUT3 的基因和蛋白表达谱：巴西本地人群、METABRIC 和 TCGA。通过实时 PCR 和 Western blot 分别测量巴西人群中的 FUT3 转录本和蛋白。通过 CBioPortal 数据库访问公共 METABRIC 和 TCGA 队列的临床记录和 FUT3 水平。使用适当的统计工具分析每个队列中的 FUT3 表达。使用包括 GSE41119、GSE47994 和 GSE86945 在内的五个独立队列对三阴性患者进行生存荟萃分析，这些数据来自 NCBI 数据库中 GEO 存储库，以及 METABRIC 和 TCGA。我们的分析表明，高 FUT3 水平与浸润性乳腺癌患者的总体生存率降低始终相关。这一发现在三阴性患者中尤为显著。这些结果以及先前关于 FUT3 参与促肿瘤和抗肿瘤机制的知识，促使我们提出了 FUT3 表达在乳腺癌建立和进展过程中调控的模型。
