Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer

So-Woon Kim,Sung-Im Do,Kiyong Na,Jinah Chu

doi:10.3390/medicina57080837

So-Woon Kim, Sung-Im Do + Show 2 more

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https://doi.org/10.3390/medicina57080837

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Abstract

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.

Highlights

Breast cancer is the most common malignancy among women worldwide and is a leading cause of cancer-related deaths
Low expression of Kidney and brain protein (KIBRA) was significantly associated with poor event-free survival (EFS) (p = 0.041, hazard ratio (HR) = 1.658, 95% confidence interval [CI] = 1.015–2.709), when compared to the EFS of KIBRA-high patients (Table 3)
We found a prognostic effect of KIBRA in patients with breast cancer, especially in patients with estrogen receptor (ER)-negative cancer containing the human epidermal growth factor receptor 2 (HER2)-enriched and TBNC subtypes

Summary

Introduction

Breast cancer is the most common malignancy among women worldwide and is a leading cause of cancer-related deaths. 15% of breast cancers are diagnosed as triple-negative breast cancer (TNBC), and there are no approved targeted therapies for TNBC, leading to poor prognosis [2,3,4]. In this regard, concerted efforts have been made to understand the molecular basis of TNBC heterogeneity and discover actionable targets [4]. Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. Our data highlight KIBRA expression status as a potential prognostic marker for TNBC

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