Prediction of survival prognosis of non-small cell lung cancer by APE1 through regulation of Epithelial-Mesenchymal Transition.

Xi Wei,Ming Gao,Sheng Zhang,Chongbiao Huang,Xiaojie Xin,Wei Duan,Jingtao Luo,Qing Li,Dong Wang,Xiangqian Zheng,Lei Sun,Ying Li

doi:10.18632/oncotarget.8660

Abstract

The DNA base excision repair gene APE1 involves in DNA damage repair pathway and overexpression in a variety of human cancers. Analyses of patients with non-small cell lung cancer (NSCLC) suggested that multiple factors associated with prognosis of NSCLC patients. Further investigation showed that APE1 expression was able to predict the progression-free survival and overall survival in patients with NSCLC and correlated with lymph node metastasis. Intriguingly, as a stratification of APE1-141 SNPs in APE1 positive expression, we also found APE1-141 GT/GG was identified as a marker for prediction of poor survival in NSCLC patients. In the in vitro experiments, the results showed that when APE1 expression was inhibited by siRNA or AT101 (an APE1 inhibitor), the migration and invasion of NSCLC cells were suppressed. Furthermore, epithelial-mesenchymal transition (EMT) markers was tested to provide evidence that APE1 promoted NSCLC EMT through interaction with SirT1. Using NSCLC xenograft models, we confirmed that AT101 shrank tumor volumes and inhibited lymph node metastasis. In conclusion, APE1 could be a potential target for patients with NSCLC metastasis and AT101 is a potent inhibitor in further treatment of NSCLC patients.

Highlights

The non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer [1, 2]
The characteristics of patients with NSCLC involved in lymph node metastasis The clinical outcomes of patients with NSCLC were analyzed after surgery based on the final pathological diagnosis
We found that lymph node involvement was correlated with TNM stage or chemotherapeutic toxicity and considered as an independent factor in prediction of survival of NSCLC patients

Summary

Introduction

The non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer [1, 2]. Patients with NSCLC are prone to lymph node metastasis at the advanced stage [3, 4]. Systemic lymphadenectomy has been recognized as a vital treatment of NSCLC with lymph node metastasis, millions of death still happens annually www.impactjournals.com/oncotarget [3, 5]. Apurinic/apyrimidinic endonuclease 1 (APE1) have function of DNA damage repair and protein reductionoxidation [6, 7]. It is a transcriptional co-activator of numerous pathways, including NF-KB, Myb, HIF-1a, PAX, p53 and AP-1 [7, 8]. The APE1-141 GG homozygous genotype protected against lung cancer risk reported by Peng Y et al [10]

Methods

Results

Conclusion