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Prognostic Significance of Erythrocyte protein band 4.1-like5 Expression in Upper Urinary Tract Urothelial Carcinoma

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Sources of Funding: none

Introduction

The erythrocyte protein band 4.1-like5 (EPB4.1L5) regulates E-cadherin in cancer invasion and metastasis inducing epithelial to mesenchymal transition (EMT). EPB4.1L5 coordinates the downregulation of E-cadherin-mediated cell-cell adhesion in a posttranscriptional manner by binding to p120 catenin, inhibiting p120 catenin-E-cadherin binding, and relocalizing E-cadherin by endocytosis. Recently, it is reported that in the breast cancer cells ZEB1, one of EMT transcriptional factors, induces EPB4.1L5 and promotes tumor invasion and metastasis. This study aimed to investigate the biological significance of EPB4.1L5 in upper urinary tract urothelial carcinoma (UTUC).

Methods

Retrospective analysis of the clinical records of 165 patients with UTUC (Ta-4N0M0) subjected to radical nephroureterectomy and immunohistochemical examination of EPB4.1L5 expression in those tissues.

Results

The median follow-up period was 62.2 months. The score of EPB4.1L5 significantly correlated with tumor grade, pathological T stage, and lymphovascular invasion (all p<0.001). The 5-year Kaplan–Meier recurrence-free survival and cancer-specific survival rates were 59.5% and 54.1% in patients with high EPB4.1L5 expression, compared with 81.6% and 87.2%,(all p<0.001) in their counterparts. Multivariate analyses revealed that high expression of EPB4.1L5 was one of the independent prognostic factors for tumor recurrence (p = 0.022, HR = 2.40) and cancer specific survival (p = 0.015, HR = 2.94).

Conclusions

High EPB4.1L5 expression related to worse clinical outcome in patients with UTUC. These results indicated that EPB4.1L5 could provide prognostic information in patients with UTUC regarding EMT.

Funding

none

Authors
Tatsuaki Daimon
Takeo Kosaka
Eiji Kikuchi
Shuji Mikami
Yasumasa Miyazaki
Ryuchi Mizuno
Akira Miyajima
Yasunori Okada
Hisataka Sabe
Mototsugu Oya
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