Clinical Relevance of Liver Kinase B1(LKB1) Protein and Gene Expression in Breast Cancer.

I-Chun Chen,Ann-Lii Cheng,Yen-Shen Lu,Tzu-Pin Lu,Kuan-Ting Kuo,Wen-Hung Kuo,Ching-Hung Lin,Ming-Yang Wang,Tsu-Hsin Hsueh,Yuan-Ching Chang,Kuei-Pin Chung,Chen-Yang Shen,Pei-Fang Wu,Chiun-Sheng Huang

doi:10.1038/srep21374

Abstract

Liver kinase B1 (LKB1) is a tumor suppressor, and its loss might lead to activation of the mammalian target of rapamycin (mTOR) and tumorigenesis. This study aimed to determine the clinical relevance of LKB1 gene and protein expression in breast cancer patients. LKB1 protein expression was evaluated using immunohistochemistry in tumors from early breast cancer patients in two Taiwanese medical centers. Data on LKB1 gene expression were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data set. The correlations between LKB1 expression, clinicopathologic factors, and patient outcome were analyzed. LKB1 expression was significantly associated with estrogen receptor (ER) expression in 2 of the 4 cohorts, but not with other clinicopathologic factors. LKB1 expression was not a predictor for relapse-free survival, overall survival (OS), or breast cancer-specific survival. In a subgroup analysis of the two Taiwanese cohorts, high LKB1 protein expression was predictive of high OS in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients (P = 0.013). Our study results indicate that LKB1 expression is not prognostic in the whole population of breast cancer patients, but it is a potential predictor of OS in the subset of HER2-positive patients

Highlights

A previous study evaluated Liver kinase B1 (LKB1) expression in metastatic estrogen receptor (ER)-positive breast cancer samples (n = 55) from the TAMRAD trial6,and observed that low LKB1 expression was predictive of everolimus efficacy
We investigated the role of LKB1 in breast cancer by evaluating LKB1 protein expression in 2 Asian cohorts using immunohistochemistry (IHC) stain, and by evaluating LKB1 gene expression in microarray data sets from 2 Western cohorts[9]
The numbers of stage I–III patients from the 4 cohorts included in final analyses of clinicopathologic factors and survival status were, sequentially, 569 (NTUH), 277 (MMH), 988 (METABRIC discovery), and 975 (METABRIC validation)

Summary

Introduction

This study is the only human study to indicate the predictive value of LKB1 in targeted therapy for breast cancer. Two studies have evaluated the prognostic value of LKB1 in breast cancer patients. In Bouchekioua-Bouzaghou et al.[8], high cytoplasmic LKB1 expression was associated with low disease-free survival (DFS) in a cohort of 154 breast cancer patients. In 2 human breast cancer studies, ER expression was associated with low LKB18 and high LKB15 expression. These studies have had relatively small samples The results have indicated that LKB1 might play a key role in breast cancer biology; its relationships with survival and ER status warrant further investigation. We assessed the predictive value of LKB1 for survival outcomes according to various risk and prognostic groups

Objectives

Methods

Results

Conclusion