Circulating plasma microRNAs as potential markers to identify EGFR mutation status and to monitor epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with advanced non-small cell lung cancer.

Lili Qu,Jianjie Li,Hongjun Gao,Shaoxing Yang,Hong Wang,Lin Wang,Xiaoqing Liu,Chuanhao Tang,Panpan Lv,Weixia Wang,Xiaoyan Li,Yangyang Lei,Haifeng Qin,Hanjiang Fu,Xiaofei Zheng,Min Zhang,Guanhua Zhao,Santai Song,Liangliang Li

doi:10.18632/oncotarget.17416

Abstract

We aimed to identify a panel of circulating plasma microRNAs that can predict EGFR mutation status and monitor epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with non-small cell lung cancer. Microarrays were performed for the preliminary screening of dysregulated microRNAs in 9 EGFR mutation-positive patients versus healthy controls. MiR-107 was upregulated and miR-195 was downregulated in the exon 19 deletion versus wild-type group. The areas under the receiver operating characteristic curves for miR-107, miR-195, and a panel of these 2 microRNAs were 0.72, 0.75, and 0.74, with sensitivities and specificities of 64.7% and 76.6%, 71.8% and 69.1%, and 71.7% and 78.9%, respectively. MiR-122 was significantly upregulated in the p.L858R versus wild-type group. An area under the receiver operative characteristic curve of 0.75 suggests that miR-122 might be a specific biomarker for patients with the p.L858R mutation. In addition, dynamic changes in these 3 microRNAs were also found to correlate with responses to epidermal growth factor receptor-tyrosine kinase inhibitor treatment, indicating that circulating plasma microRNAs may represent potential biomarkers for monitoring epidermal growth factor receptor-tyrosine kinase inhibitor treatment. This study demonstrates the prospective application of circulating plasma microRNAs as potential non-invasive, convenient biomarkers for patients with EGFR-sensitive mutations.

Highlights

As one of the most frequently diagnosed cancers, lung cancer continues to represent the first leading cause of cancerrelated mortality worldwide [1, 2]
We aimed to identify a panel of circulating plasma microRNAs that can predict EGFR mutation status and monitor epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with non-small cell lung cancer
With the exception of smoking status, no significant differences in clinical characteristics were observed between the Non-small cell lung cancer (NSCLC) patients and healthy controls or between subgroups of the NSCLC patients stratified according to EGFR mutation status

Summary

Introduction

As one of the most frequently diagnosed cancers, lung cancer continues to represent the first leading cause of cancerrelated mortality worldwide [1, 2]. Non-small cell lung cancer (NSCLC) accounts for approximately 80.0–85.0% of all lung cancers and remains a significant public health problem in China [1]. The majority of NSCLC patients are www.impactjournals.com/oncotarget diagnosed at advanced stages with poor prognoses, especially in those treated with traditional chemotherapy regimens [3]. The EGFR gene remains the most important oncogenic driver of NSCLC and treatment-naïve patients with advanced NSCLC harboring specific EGFR-sensitive mutations (principally EGFR exon 19 deletions and EGFR exon 21 p.L858R point mutations that account for approximately 45.0% and 40.0% of patients, respectively) are recommended to receive first-line epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as per the National Comprehensive Cancer Network guidelines [4,5,6]. It is crucial to identify the genotype of the tumor after the histopathological classification is determined to predict the sensitivity or resistance to an increasing number of EGFR-TKIs

Objectives

Methods

Results