Abstract
Apurinic/apyrimidinic endonuclease 1 (APE1), which has the dual functions of both DNA repair and redox activity, has been reported to be highly expressed in non-small cell lung cancer (NSCLC), and this appears to be a characteristic related to chemotherapy resistance. In this study, we identified serum APE1 autoantibodies (APE1-AAbs) in NSCLC patients and healthy controls by immunoblotting and investigated the expression of APE1-AAbs by indirect ELISA from the serum of 292 NSCLC patients and 300 healthy controls. In addition, serum APE1-AAbs level alterations of 91 patients were monitored before and after chemotherapy. Our results showed that serum APE1-AAbs can be detected in both NSCLC patients and healthy controls. Serum APE1-AAbs were significantly higher than those of healthy controls and closely related to APE1 antigen levels both in tumor tissues and the peripheral blood. Moreover, the change in levels of serum APE1-AAbs in NSCLC is closely associated with the response to chemotherapy. These results suggest that APE1-AAbs is a potential tumor marker and predictor of therapeutic efficacy in NSCLC.
Highlights
With its increasing incidence and mortality, lung cancer has become the largest cause of cancer deaths and a challenging clinical problem worldwide [1,2]
DNA repair proteins play critical roles in maintaining genomic stability and in the progression of lung cancer [32,33]. Both antigens and autoantibodies to antigens involved in DNA repair pathways, such as p53 [34,35,36] and Ku [37,38,39], have been highlighted as factors involved in tumorigenesis and as biomarkers in lung cancer, breast cancer, and leukemia
As one of the DNA repair proteins, apyrimidinic endonuclease 1 (APE1) plays an important role in cell survival, and its high expression is correlated with tumor characteristics [40,41]
Summary
With its increasing incidence and mortality, lung cancer has become the largest cause of cancer deaths and a challenging clinical problem worldwide [1,2]. Non-small cell lung cancer (NSCLC) is the main type of lung cancer, which is often diagnosed at an advanced stage so that patients have little prospect of effective and curative treatment, and this manifests with 5-year survival rates of ,15% [3]. Screening for early NSCLC biomarkers, development of therapeutic efficacy predictors, and new drugs are vital factors in improving both the patients’ prognoses and survival [4,5]. The present biomarkers and predictors for NSCLC still lack adequate sensitivity and specificity [6]. The carcinoembryonic antigen is one of the most widely-studied tumor markers in NSCLC, with an overall sensitivity of only approximately 40% [7]. More studies are required to discover novel biomarkers for assisting in the screening of NSCLC, which will greatly improve the therapeutic outcome of this malignant disease [9]
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