FOXO3A Expression in Upper Tract Urothelial Carcinoma

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

doi:10.3389/fonc.2021.603681

FOXO3A Expression in Upper Tract Urothelial Carcinoma

Front Oncol. 2021 Apr 20:11:603681. doi: 10.3389/fonc.2021.603681. eCollection 2021.

Authors

Guoyao Zhang¹, Wanping Shi², Enzhao Jia³, Lei Zhang¹, Yongsheng Han⁴, Ronald Rodriguez⁵, Tianjiang Ma¹

Affiliations

¹ Department of Oncology, Luohe Central Hospital, The First Affiliated Hospital of Luohe Medical College, Luohe, China.
² Department of Oncology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
³ Department of Pathology, Luohe Central Hospital, The First Affiliated Hospital of Luohe Medical College, Luohe, China.
⁴ Department of General Surgery, School of Medicine, Qinghai University, Xining, China.
⁵ Department of Urology, University of Texas Health Science Center San Antonio, San Antonio, TX, United States.

Abstract

Background: Epidemiological 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.

Methods: The 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.

Results: The 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.

Conclusion: Our 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.

Keywords: FOXO3A; overall survival; prognosis; recurrence-free survival; upper tract urothelial carcinoma.