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. 2024 Jun 28;15(1):250.
doi: 10.1007/s12672-024-01120-y.

FUT11 expression in gastric cancer: its prognostic significance and role in immune regulation

Yanqing Huang  1   2 , Xiaoying Yang  1   2 , Mengda Wei  1   2 , Xi Yang  1   2 , Zhenmin Yuan  1   2 , Junjie Huang  1   2 , Junren Wei  1   2 , Lei Tian  3   4
Affiliations

FUT11 expression in gastric cancer: its prognostic significance and role in immune regulation

Yanqing Huang et al. Discov Oncol. .

Abstract

Background: Gastric cancer (GC) is a malignant digestive tract tumor with a high recurrence rate and poor prognosis. Fucosylation is important in tumor glycosylation, in which the key enzyme is fucosyltransferase (FUT). FUT11 is a member of the fucosyltransferase family and has been closely associated with the development of multiple cancers. However, the specific relationship between FUT11 and GC prognosis and its molecular mechanism has not been fully studied. This study explored FUT11 expression, clinical correlation, and its role in GC occurrence and development to deepen understanding of its function.

Methods: FUT11 expression in 33 cancers was preliminarily analyzed using the Tumor Immunoassay Resource (TIMER2.0) database. FUT11 expression in GC was evaluated using The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and Gene Expression Profiling Interactive Analysis (GEPIA2) data and verified using the Gene Expression Omnibus (GEO) GSE65801 dataset. Furthermore, we studied the survival prognosis of FUT11 in GC and analyzed its effect on the survival rate of patients with GC using the KM-plotter. We also performed COX regression analysis on TCGA GC clinical data and analyzed FUT11 expression in the pathway using the STRING and LinkedOmics databases. Moreover, the relationship between FUT11 and GC immune infiltration level was examined, and the Kaplan-Meier survival analysis diagram was constructed. The FUT11 genetic variation information was retrieved using cBioPortal, and its drug sensitivity was analyzed using CellMiner. Finally, differential FUT11 expression in GC tissues was verified using immunohistochemistry.

Results: The data mining and analysis demonstrated that FUT11 expression was abnormally elevated in GC tissues and correlated with poor patient prognosis. The FUT11 expression level was an independent prognostic factor for GC. The difference in FUT11 expression level resulted in different degrees of immune cell infiltration in the patients with GC, which might regulate the tumor microenvironment. FUT11 affected GC development by participating in cancer pathways such as PI3K-AKT, neuroactive ligand-receptor, and MAPK. Immunohistochemical staining revealed that FUT11 was highly expressed in GC.

Conclusions: This study revealed that FUT11 expression is significantly increased in GC tissues. This increase is associated with poor prognosis and might affect immune regulation. FUT11 might have immunological and targeted therapeutic value, providing a new approach to GC treatment.

Keywords: Bioinformatics; FUT11; Fucosylation; GC; Immunology.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
FUT11 is highly expressed in GC tissues. A Based on the GEO-GSE65801 dataset, differential expression of FUT11 in gastric cancer and adjacent tissues (P < 0.05); B Based on the GEPIA2 database, differential expression of FUT11 in gastric cancer and adjacent tissues (P < 0.05); C Differential expression of FUT11 in gastric cancer and adjacent tissues based on TCGA-STAD (P < 0.05); D The expression differences of FUT11 in cancer tissues and adjacent tissues of different cancer species in the TIMER2 database. (* P < 0.05, * * P < 001, * * * P < 0.001, * * * P < 0.0001)
Fig. 2
Fig. 2
Survival analysis of high and low expression of FUT11 in GC patients. A Based on the GEPIA2 database, survival curves (OS) of GC patients with high and low expression of FUT11; B Time dependent ROC curves (1, 3, 5 years) of FUT11 in GC patients based on TCGA-STAD; C Based on the GEPIA2 database, heatmaps for survival analysis of high and low expression of FUT11 in different cancers
Fig. 3
Fig. 3
Functional enrichment of FUT11 protein interaction network and hub gene and their diagnostic ROC in GC. A PPI interaction network diagram of FUT11. B The top 10 hub genes of the PPI interaction network; C GO/KEGG enrichment analysis of FUT11 and hub genes; D–I Diagnostic ROC of FUT11 and hub gene
Fig. 4
Fig. 4
Enrichment analysis of FUT11 co expressed genes in GC. A The top 50 genes positively correlated with FUT11; B The top 50 genes negatively correlated with FUT11; C Biological processes related to the function of the FUT11 gene (BP); D KEGG enrichment analysis between co expressed genomes with FUT11 based on the Linkedomics database
Fig. 5
Fig. 5
Analysis of FUT11 expression and infiltration of various immune cells. A Scatter plot of the correlation between FUT11 and tumor purity, B cells, CD4+ cells, CD8+ cells, dendritic cells, macrophages, and neutrophils based on TIMER2; B Differences in abundance between high and low expression groups of FUT11 and 24 types of immune cells; C The correlation between 24 types of immune cells and FUT11 expression
Fig. 6
Fig. 6
HR and p-value forest plots of FUT11 expression in KM survival analysis of gastric cancer patients under different immune cell subsets
Fig. 7
Fig. 7
Genetic mutations in FUT11 in the cBioPortal database. A Histograms of FUT11 mutations in 32 types of cancer; B FUT11 mutation map across protein domains
Fig. 8
Fig. 8
Drug sensitivity analysis of FUT11 gene expression. A–T Scatter plot of the correlation between high expression of the FUT11 gene and Irofulven, Teriflunomide, Deforolimius, Quizartinib, Sonidegib, Ipataserib, Idealisib, endosplenitib, Bendamustine, ciclosporin, Cyclophosphamide, Chelsea, Artemether, Entinostat, Palbociclib, tic10, Dexrazoxane, Dacarbazine, Ifosfamide, Imexon
Fig. 9
Fig. 9
The expression of FUT11 in human gastric cancer and adjacent tissues. A Semi quantitative analysis (AOD value) of FUT11 in GC and adjacent tissues (IHCx200) (* * * * P < 0.0001). B The expression of FUT11 in gastric cancer tissues with different pathological stages and Ki-67 expression
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