FUT10 is related to the poor prognosis and immune infiltration in clear cell renal cell carcinoma.

Abstract

Background: Clear cell renal cell carcinoma (ccRCC), is highly metastatic with unfavorable oncologic outcomes. The metastatic dissemination and underlying mechanisms of ccRCC remain insufficiently understood. The expression of fucosyltransferases (FUTs) has been explored in multiple cancer types, which affect survival of tumor cells and oncology progress. However, the role of fucosyltransferase 10 (FUT10), a member of the FUT family, is still unclear in ccRCC. We aimed to investigate the effects of FUT10 on the prognosis and immune infiltration of ccRCC via The Cancer Genome Atlas (TCGA) database.

Methods: The relationship between FUT10 expression and clinical-pathologic features was evaluated by Welch's t-test, Wilcoxon signed-rank test, Dunn's test, and logistic regression based on TCGA datasets. The FUT10 expression level was converted into a categorical variable by receiver operating characteristic (ROC) and the area under the curve (AUC). The factors associated with the prognosis were determined by Kaplan-Meier method. The function of FUT10 was identified by functional enrichment analysis, gene set enrichment analysis (GSEA), gene correlation analysis, and immune infiltration analysis. At last, we verified the FUT10 messenger RNA (mRNA) expression in ccRCC and adjacent kidney tissues by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Downregulated FUT10 expression in ccRCC was associated with the clinical stage (P<0.001), T stage (P<0.001), M stage (P<0.001), and overall survival (OS) event (P<0.001). The ROC curve suggested that FUT10 had a certain accuracy in the diagnostic ability in ccRCC (AUC =0.787). It was shown that patient survival was prolonged in the FUT10 high-expression group. Meanwhile, multivariate analysis displayed that FUT10 was an independent risk factor for ccRCC patients (P=0.003). Moreover, we uncovered that FUT10 was involved in the phenotype of the immune response, oxidative phosphorylation (OXPHOS), arachidonic acid (AA) metabolism, and primary immunodeficiency (PID) by function enrichment analysis and GSEA. In addition, in the high FUT10 expression group, natural killer (NK) CD56bright cells exhibited lower enrichment scores, and central memory T cells exhibited higher enrichment scores. Especially, ARL8B, a key factor in NK-mediated cytotoxicity, had a certain correlation with FUT10 (r=0.590, P<0.001). Compared to the normal kidney tissues, the FUT10 mRNA expression in the ccRCC was decreased (P=0.004).

Conclusions: FUT10 might be a promising immune therapy target and prognostic biomarker in ccRCC.