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


METHODS
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.
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Shiheng
S
Zhang
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Le
L
He
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Nan
N
Dai
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Wei
W
Guan
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Jinlu
J
Shan
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Xueqin
X
Yang
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Zhaoyang
Z
Zhong
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Yi
Y
Qing
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Feng
F
Jin
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Chuan
C
Chen
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Yuxin
Y
Yang
Department of Pathology, Baylor University Medical Center, Dallas, TX 75246, USA.
Hongyi
H
Wang
Department of Pathology, Baylor University Medical Center, Dallas, TX 75246, USA.
Laura
L
Baugh
Laboratory of Molecular Biology and DNA repair, Department of Medical and Biological Sciences, University of Udine, Udine 33100, Italy.
Gianluca
G
Tell
Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
David M
DM
Wilson
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Mengxia
M
Li
Cancer Center of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Dong
D
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D010984:Platinum; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
APE1; NSCLC; biomarker; chemotherapy