FOXO3A Expression in Upper Tract Urothelial Carcinoma.

Guoyao Zhang,Ronald Rodriguez,Yongsheng Han,Enzhao Jia,Tianjiang Ma,Lei Zhang,Wanping Shi

doi:10.3389/fonc.2021.603681

Abstract

BackgroundEpidemiological studies have reported various results regarding whether FOXO3A is related to various carcinomas. However, the prognostic significance of FOXO3A in upper tract urothelial carcinoma (UTUC) remains unclear. The purpose of this study was to validate the correlation between FOXO3A expression and oncological outcomes in UTUC.MethodsThe expression levels of FOXO3A in 107 UTUC patients were examined by immunohistochemistry (IHC). We examined the prognostic role of FOXO3A by using the Cox proportional hazard model.ResultsThe results indicated that FOXO3A expression was notably decreased in UTUC tissue compared with control tissue. Decreased expression of FOXO3A was also related to advanced pathologic stage (P = 0.026), lymph node metastasis (P = 0.040), lymphovascular invasion (P < 0.001), and adjuvant therapy (P = 0.048). In addition, UTUC patients with low FOXO3A expression had a significantly shorter survival time, including both overall survival (OS) [hazard ratio (HR) 2.382, P = 0.004] and recurrence-free survival (RFS) (HR 2.385, P = 0.004), than those with high expression. Multivariate analyses showed that FOXO3A was a significant predictor for OS (HR 2.145, P = 0.014) and RFS (HR 2.227, P = 0.010) in UTUC patients.ConclusionOur results indicate that FOXO3A may be involved in the recurrence of UTUC and that it has certain clinical value in the therapeutic targeting and prognostic evaluation of UTUC.

Highlights

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract
Expression of Forkhead box O 3a (FOXO3A) Protein Is Decreased in upper tract UCs (UTUCs) Patients
The expression of FOXO3A was lower in UTUC patients than in normal tissues (UTUC vs normal tissues: 13/40 vs. 22/40, P < 0.001)

Summary

Introduction

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract. upper tract (renal pelvis and ureter) tumors account for only 5% to 10% of all UCs, and almost 60% of upper tract UCs (UTUCs) are invasive at diagnosis [1, 2]. FOXO3A activity and stability can be regulated by post−translational modifications, including phosphorylation, acetylation, ubiquitination and glycosylation, aside from its well-validated modifications in transcription [7]. It has been highlighted as an important transcriptional regulator of crucial proteins participating in DNA damage repair [8], cell cycle regulation [9], apoptosis [10], angiogenesis [11], and cellular stress response [12]. The prognostic significance of FOXO3A in upper tract urothelial carcinoma (UTUC) remains unclear. The purpose of this study was to validate the correlation between FOXO3A expression and oncological outcomes in UTUC

Objectives

Methods

Results

Conclusion