Serum APE1 Autoantibodies: A Novel Potential Tumor Marker and Predictor of Chemotherapeutic Efficacy in Non-Small Cell Lung Cancer

<div><p>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.</p> </div

Characteristics and serum APE1-AAbs distribution of NSCLC patients with pre- and post- chemotherapy.

<p><i>p</i> value were obtained after comparing the levels APE1-AAbs of pre- and post- chemotherapy, as determined by paired <i>t</i>-test.</p

Distribution of serum APE1-AAbs before and after chemotherapy.

<p>The serum APE1-AAbs level was much higher in the poor chemotherapeutic response group than in the good response group (<i>p</i> = 0.000). There was a significant difference in the group with good platinum-based chemotherapeutic response before and after chemotherapy (<i>p</i><0.001), while there was no difference in the group with poor platinum-based chemotherapeutic response before and after chemotherapy (<i>p</i> = 0.393). *before chemotherapy versus after chemotherapy (<i>p</i><0.001). <i>p</i> value were obtained after comparing the levels APE1-AAbs of pre- and post- chemotherapy, as determined by paired <i>t</i>-test.</p

Clinical characteristics and distribution of sera APE1-AAbs of studied groups.

<p><i>p</i> values were calculated using chi-square test.</p

Association of serum APE1-AAbs level with clinical characteristics among NSCLC groups.

<p>Adeno: adenocarcinoma; LCLC: large cell lung cancer. Independent <i>t</i>-test and ANOVA were used to analyze associations between the APE1-AAbs level (OD) and clinical characteristics. Chi-square test was used to analyze associations between the APE1-AAbs positive and clinical characteristics.</p>*<p>Adeno versus Squamous; a: I+II versus III; b: III versus IV; c: I+II versus IV.</p

Dot blot and Western blot for identifying serum APE1-AAbs.

<p>A, Representative results of detection of sera APE1-AAbs by dot blot assay. Lanes 1∼5: serum of healthy subjects. Lanes 6∼10: serum of NSCLC patients. B, Serum APE1-AAbs of healthy and NSCLC patients were detected by Western blot analysis. Lane M, protein molecular weight markers; APE1, APE1 fusion protein with His tag; A549, total cell protein extracted from A549 cells; Anti-His, APE1 fusion protein detected by His antibody.</p

Receiver operating characteristic curves for APE1-AAbs level for NSCLC detection.

<p>Serum concentrations of APE1-AAbs levels among 292 NSCLC patients and 300 healthy controls were determined by ELISA. The diagnostic potentials of APE1-AAbs were assessed by ROC curves. The AUC value was 0.745.</p

Additional file 1: of Central nervous system progression in advanced non–small cell lung cancer patients with EGFR mutations in response to first-line treatment with two EGFR-TKIs, gefitinib and erlotinib: a comparative study

The raw clinical data of current study. (XLSX 57 kb