Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

// Shiheng Zhang 1, * , Le He 1, * , Nan Dai 1 , Wei Guan 1 , Jinlu Shan 1 , Xueqin Yang 1 , Zhaoyang Zhong 1 , Yi Qing 1 , Feng Jin 1 , Chuan Chen 1 , Yuxin Yang 1 , Hongyi Wang 4 , Laura Baugh 4 , Gianluca Tell 2 , David M. Wilson III 3 , Mengxia Li 1 , Dong Wang 1 1 Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China 2 Laboratory of Molecular Biology and DNA repair, Department of Medical and Biological Sciences, University of Udine, Udine 33100, Italy 3 Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA 4 Department of Pathology, Baylor University Medical Center, Dallas, TX 75246, USA 5 Tianjin HUABOTE Biotechnological Inc., Tianjin 300350, China * These authors contributed equally to this work Correspondence to: Mengxia Li, email: mengxia.li@outlook.com Dong Wang, email: dongwang64@hotmail.com Keywords: APE1, NSCLC, chemotherapy, biomarker Received: March 17, 2016 Accepted: October 14, 2016 Published: November 02, 2016 ABSTRACT Purpose: To define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy. Results: Our investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue ( r 2 = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2.165, p < 0.001, HR: 1.421, p = 0.012), but not with overall survival. After 6 cycles of chemotherapy, a low APE1 serum level was associated with better overall survival (HR: 0.497, p = 0.010). Experimental Design: We measured APE1 protein levels in biopsy tissue from 172 NSCLC patients and sera of 412 NSCLC patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. APE1 levels in sera of 523 healthy donors were also determined as control. Conclusions: Our studies indicate that APE1 is a biomarker for predicting prognosis and therapeutic efficacy in NSCLC. The chemotherapy-naive serum APE1 level, which correlated with its tissue level inversely associated with progression-free survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival.