Research Papers:

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

Shiheng Zhang, Le He, Nan Dai, Wei Guan, Jinlu Shan, Xueqin Yang, Zhaoyang Zhong, Yi Qing, Feng Jin, Chuan Chen, Yuxin Yang, Hongyi Wang, Laura Baugh, Gianluca Tell, David M. Wilson III, Mengxia Li and Dong Wang _

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Oncotarget. 2016; 7:77482-77494. https://doi.org/10.18632/oncotarget.13030

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Shiheng Zhang1,*, Le He1,*, Nan Dai1, Wei Guan1, Jinlu Shan1, Xueqin Yang1, Zhaoyang Zhong1, Yi Qing1, Feng Jin1, Chuan Chen1, Yuxin Yang1, Hongyi Wang4, Laura Baugh4, Gianluca Tell2, David M. Wilson III3, Mengxia Li1, Dong Wang1

1Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China

2Laboratory of Molecular Biology and DNA repair, Department of Medical and Biological Sciences, University of Udine, Udine 33100, Italy

3Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA

4Department of Pathology, Baylor University Medical Center, Dallas, TX 75246, USA

5Tianjin HUABOTE Biotechnological Inc., Tianjin 300350, China

*These authors contributed equally to this work

Correspondence to:

Mengxia Li, email: [email protected]

Dong Wang, email: [email protected]

Keywords: APE1, NSCLC, chemotherapy, biomarker

Received: March 17, 2016     Accepted: October 14, 2016     Published: November 02, 2016


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 (r2 = 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-naïve 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.

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