Abstract
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.
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Acknowledgments
We gratefully acknowledge Dr. George Siqueira and all the clinical and technical team from Hospital das Clínicas da Universidade Federal de Pernambuco (HC-UFPE, Brazil) for the support during the volunteers’ screening and sample collection. We also thank Professor Dayane Gomes from Universidade Federal de Pernambuco (Brazil) for the support during the execution of the Western blotting platform assays and Dr. Sandra L. Romero Cordoba from Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran (Mexico) to provide us the clinical data from GSE86945 cohort.
Funding
This study was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant number 480291/2011–0]; and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jessica Catarine Frutuoso do Nascimento. The first draft of the manuscript was written by Jessica Catarine Frutuoso do Nascimento and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee (Comité de Ética em Pesquisa Envolvendo Seres Humanos do Centro de Ciências da Saúde da Universidade Federal de Pernambuco, CAAE 06586612.9.0000.5208 — Num. 140.876) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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do Nascimento, J.C.F., Beltrão, E.I.C. & Rocha, C.R.C. High FUT3 expression is a marker of lower overall survival of breast cancer patients. Glycoconj J 37, 263–275 (2020). https://doi.org/10.1007/s10719-020-09914-2
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DOI: https://doi.org/10.1007/s10719-020-09914-2