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FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

Authors Liu M, Zheng Q, Chen S, Liu J, Li S

Received 11 December 2020

Accepted for publication 10 February 2021

Published 25 March 2021 Volume 2021:14 Pages 1069—1084

DOI https://doi.org/10.2147/JIR.S296597

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Professor Ning Quan


Mulin Liu,1,* Qin Zheng,2,* Siyi Chen,2 Jiwei Liu,3 Shijun Li1

1Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning Province, 116044, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Shijun Li
Director of Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, Liaoning Province, 116011, People’s Republic of China
Tel +86-0411-83635963-2232
Fax +86-0411-83622844
Email [email protected]
Jiwei Liu
Director of Department of Oncology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, Liaoning Province, 116011, People’s Republic of China
Tel +86-0411-83635963-2232
Fax +86-0411-83622844
Email [email protected]

Background: Bladder urothelial carcinoma (BLCA) is one of the most frequently appearing, lethal and aggressive malignancies of the genitourinary system with growing morbidity and mortality, which affects human health seriously. Protein glycosylation, catalyzed by specific glycosyltransferase, has been found to be abnormal in several diseases, especially cancer. Fucosyltransferase VII (FUT7), one of the fucosyltransferases, was observed abnormally expressed in various cancers, however, the role of FUT7 in BLCA, and the association between its expression and clinical outcomes or immune infiltration remains unclear.
Methodology: FUT7 expression in BLCA was analyzed in Oncomine database, which was further confirmed with immunohistochemistry and ELISA. The prognostic value of FUT7 for BLCA was evaluated with PrognoScan database, and its genetic alteration was examined in cBioPortal database. The proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) changes of bladder cancer cells after FUT7 siRNA or cDNA transfection were determined by CCK8, colony formation, transwell and Western blot, respectively. The correlation between FUT7 expression and immune infiltration levels was analyzed in TIMER and TISIDB databases, and the methylation level of FUT7 was detected in UALCAN database.
Results: The results showed that the expression of FUT7 was increased in BLCA, and patients with high FUT7 level were predicted to have lower overall survival and disease-specific survival rates, which were not influenced by FUT7 genetic alterations. Downregulation FUT7 inhibited the proliferation, migration, invasion and EMT of bladder cancer cells, whereas upregulation of FUT7 showed the opposite effects. We found that FUT7 was positively correlated with immune cell infiltration levels (CD8+ T cells, CD4+T cells, macrophage, neutrophil and dendritic cells), and also the expression of gene markers of immune cells. The negative correlation between FUT7 expression and FUT7 methylation level was observed, among which FUT7 expression was positively correlated with the abundance of 28 kinds of tumor-infiltrating lymphocytes (TILs), while FUT7 methylation level was negatively correlated with TILs.
Conclusion: Altogether, these findings suggested that FUT7 possessed the potential to serve as a detection biomarker or immunotherapeutic target for BLCA.

Keywords: bladder urothelial carcinoma, FUT7, EMT, diagnosis, prognosis, immune infiltration

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