Fucosyltransferases Regulated by Fusobacterium Nucleatum and Act as Novel Biomarkers in Colon Adenocarcinoma

Pengfei Wang; Xuxu Liu; Jingjing Yu; Ziang Meng; Zhenyi Lv; Ce Shang; Qi Geng; Dawei Wang; Dongbo Xue; Long Li

doi:10.2147/JIR.S396484

Fucosyltransferases Regulated by Fusobacterium Nucleatum and Act as Novel Biomarkers in Colon Adenocarcinoma

J Inflamm Res. 2023 Feb 21:16:747-768. doi: 10.2147/JIR.S396484. eCollection 2023.

Authors

Pengfei Wang^#^{1

2}, Xuxu Liu^#^{1

2}, Jingjing Yu^{1

2}, Ziang Meng^{1

2}, Zhenyi Lv^{1

2}, Ce Shang^{1

2}, Qi Geng^{1

2}, Dawei Wang^{1

2}, Dongbo Xue^{1

2}, Long Li³

Affiliations

¹ Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
² Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
³ Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Colon adenocarcinoma (COAD) is one of the leading causes of cancer-associated mortality worldwide. Fucosyltransferases (FUTs) are associated with numerous cancers. We aimed to investigate the functions of FUTs in COAD.

Patients and methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the expression and clinical relevance of FUTs in COAD. Real Time Quantitative PCR (RT-qPCR), Western blot, immunohistochemistry and ELISA were used to detect the relative RNA and protein expression levels. Colitis-associated cancer mice treated with Fusobacterium nucleatum were used to illustrate the effects of Fusobacterium nucleatum on FUTs and COAD. Luciferase reporting assay was used to investigate the binding of miRNA to mRNA.

Results: TCGA and GEO datasets showed abnormal expression of FUTs in COAD at transcript level. RT-qPCR, Western blot and immunohistochemistry showed increased expression of FUT1, POFUT1 and POFUT2 in COAD. COAD patients with a high expression of FUT1, FUT11, FUT13 (POFUT2) had a worse prognosis, while patients with a high expression of FUT2, FUT3, FUT6 had a better prognosis. FUT1 and POFUT2 could independently predict the prognosis of COAD patients. Functional analysis by CancerSEA database showed that FUT3, FUT6, FUT8, FUT12 (POFUT1) and FUT13 are associated with differentiation, apoptosis, invasion, quiescence, and hypoxia. FUTs are associated with the tumor microenvironment of COAD. FUT1 regulated by miR-939-3p inhibit the expression of MUC2. Fusobacterium nucleatum may affect the expression of FUTs by affecting their transcription factors and miRNA levels. Moreover, Fusobacterium nucleatum promotes COAD progression through the miR-939-3p/FUT1/MUC2 axis.

Conclusion: Fucosyltransferases play an important role and may be the mediator of Fusobacterium nucleatum promoting COAD progression.

Keywords: Fusobacterium nucleatum; colon adenocarcinoma; fucosyltransferases; oncological properties; prognostic.