Cytoplasmic HAX1 Is an Independent Risk Factor for Breast Cancer Metastasis.

Alicja Trebinska-Stryjewska,Lukasz Szafron,Joanna Owczarek,Anna Balcerak,Anna Felisiak-Golabek,Renata Sienkiewicz,Ewa A Grzybowska,Maciej Wakula,Alina Rembiszewska,Sylwia Tabor

doi:10.1155/2019/6375025

Alicja Trebinska-Stryjewska, Lukasz Szafron + Show 8 more

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https://doi.org/10.1155/2019/6375025

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Abstract

HAX1 is an antiapoptotic factor involved in the regulation of cell migration and calcium homeostasis, overexpressed in several cancers, including breast cancer. It has been suggested that HAX1 is also implicated in metastasis. Herein we report the results of meta-analysis of HAX1 expression, based on publicly available data, which confirms its significant overexpression in breast cancer and demonstrates copy number gain and prognostic value of HAX1 overexpression for metastatic relapse in ER+ tumors. IHC analysis reported here also reveals its significant overexpression in breast cancer samples from primary tumors, indicating significantly higher HAX1 protein levels in a group of patients who developed distant metastases in a disease course. Moreover, we demonstrate that HAX1 localization is important for the prediction of metastatic relapse and that cytoplasmic but not nuclear HAX1 is an independent risk factor for breast cancer metastasis.

Highlights

Breast cancer is the most common neoplasm and the primary cause of cancer death in women [1]
We found out that elevated HAX1 levels in the cytoplasm emerged as an independent, negative prognostic factor, associated with an increased risk of distant metastasis (HR 2.832, 95% CI 1.2076.644, p=0.017)
There were several studies reporting HAX overexpression in different types of malignancies, we showed for the first time that high HAX mRNA levels in cancer cells could be a consequence of gene amplification, at least in breast cancer

Summary

Introduction

Breast cancer is the most common neoplasm and the primary cause of cancer death in women [1]. The current 5-year survival for primary breast cancer is quite high (8092%), but, despite the advances in diagnosis and treatment of early breast cancer patients, about 20-40% experience distant organ metastases, for which the prognosis is significantly worse [4,5,6,7]. Breast cancer is heterogeneous disease and a probability to develop metastases depends on histopathological parameters (lymph node status, histologic grade, and tumor size) and on molecular subtypes defined roughly as basal-like, normal-like, HER2−enriched, and luminal A and luminal B, each of which has a different prognosis and a pattern of recurrence. Basal cancers tend to metastasize early (with a peak about 2-3 years after diagnosis) and frequently [8, 9], but typically there is no recurrence after 5 years in this subtype. Distinct pattern of metastatic relapse in basal and luminal subtypes suggests different routes for metastasis

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