High expression of FUT3 is linked to poor prognosis in clear cell renal cell carcinoma

Abstract

Background and purpose: Some of the fucosylation catalyzed by fucosyltransferase-III mediates the epithelial-mesenchymal transition and enhances tumor cell-macrophage signaling, which promotes malignant transforming and immune evasion. The aim of the study was to investigate the association between the expression of fucosyltransferase-III and clinical outcomes of patients with clear-cell renal cell carcinoma after surgery.

Results: High fucosyltransferase-III expression was associated with a greater risk of recurrence (p = 0.002) and shortened overall survival (p < 0.001). We then established a prognostic nomogram including tumor size, pathologic T, N, M stage, coagulative necrosis, lymphovascular invasion and fucosyltransferase-III expression. Furthermore, the predictive accuracy of the Leibovich prognostic score was improved when fucosyltransferase-III expression was added (p = 0.009 for overall survival and p = 0.002 for recurrence-free survival).

Materials and methods: We conducted a retrospective cohort study of 406 patients who underwent partial or radical nephrectomy between January 2008 and December 2009 in a single institute. Fucosyltransferase-III expression levels were evaluated by immunohistochemical staining in tumor tissues. Kaplan-Meier method was applied to compare survival curves. Cox regression models were fitted to analyze the effect of prognostic factors on recurrence-free and overall survival. Harrell's concordance index and Akaike's Information Criteria were calculated to assess predictive accuracy.

Conclusions: Fucosyltransferase-III is a predictive factor for poor overall survival and recurrence free survival in patients with ccRCC. The inhibitor of fucosyltransferase-III might be a potential therapeutic method for the disease.

Keywords: clear cell renal cell carcinoma; fucosyltransferase-III; overall survival; prognosis; recurrence free survival.

Figure 1. Representative photograph of FUT3 immunostaining in TMA (magnification * 200, scale bar = 100 μm)

(A) showed low densities of FUT3 while (B) showed high densities of FUT3.

Figure 2. Kaplan-Meier curves of overall survival and recurrence free survival based on tumor FUT3 expression

(A) n = 406, p < 0.001; (B) n = 394, p = 0.002.

Figure 3. Multivariate analyses of conventional prognostic features in OS and RFS

Figure 3 showed hazard ratio and p-value of each clinical and pathologic feature for OS and RFS. Abbreviation: LVI, lymphovascular invasion; ECOG-PS, Eastern cooperative Oncology Group performance status; FUT3, fucosyltransferase-III.

Figure 4. Built-up prognostic nomogram for OS prediction and calibration for it

(A) showed an eight independent prognostic factors including tumor size, pathologic T, N, M stage, the presence of coagulative necrosis and lymphovascular invasion and FUT3 expression. The total point was generated by adding the scores of the prognostic factors. (B-D) showed the calibration plot for nomogram predicted 1-year, 3-year and 5-year overall survival rate.

Figure 5. Built-up prognostic nomogram for RFS prediction and calibration for it

(A) showed a seven independent prognostic factors including tumor size, pathologic T stage, Fuhrman grade, the presence of coagulative necrosis and lymphovascular invasion and FUT3 expression. The total point was generated by adding the scores of the prognostic factors. (B-D) showed the calibration plot for nomogram predicted 1-year, 3-year and 5-year recurrence free survival rate.