APE1/Ref-1 could serve as a potential serological biomarker for the diagnosis and prognosis of oral squamous cell carcinoma

Publication date: Available online 11 December 2018

Source: Journal of Oral and Maxillofacial Surgery

Author(s): Jianli Xie, Ying Li, Jingjing Kong, Chong Li

Abstract

Objectives

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that shows elevated expression in many cancers including oral squamous cell carcinoma (OSCC), but the serum APE1/REF-1 level remains unknown in OSCC patients. The purpose of this study was to estimate serum APE/Ref-1 levels in OSCC subjects and to measure its association with the diagnosis, clinicopathological features and prognosis of OSCC.

Methods

A total of 98 primary OSCC patients and 109 age- or gender-matched normal controls were included in this case-control study. The predictor variable was serum APE1/Ref-1 level which was measured by enzyme-linked immunosorbent assay, and the outcome variables included diagnosis, clinicopathological characteristics, treatment response, and prognosis of OSCC. The optimal cut-off points of serum APE1/Ref-1 were identified by the X-tile program with minimum P values. Prognostic factors were evaluated using univariate and multivariate Cox regression models.

Results

The average age of OSCC patients were 51.6 ± 8.7 years (63 men and 35 women), and 52.4 ± 10.3 years (67 men and 42 women) of normal controls. The serum APE1/Ref-1 level was significantly higher in OSCC patients than controls (4.56 ± 1.09 ng/mL vs 3.18 ± 0.88 ng/mL; P < 0.01). Much higher serum APE1/Ref-1 levels were observed in OSCC patients with late TNM stage, lymph node metastases, and worse pathological differentiation. ROC curve analysis illustrated that the serum APE1/Ref-1 level was a potential biomarker for differentiating OSCC patients from controls with an AUC of 0.83 (95% CI 0.78–0.88, sensitivity of 0.87, and specificity of 0.68). The log-rank analysis revealed that OSCC patients with a low APE1/Ref-1 level had longer disease-free survival after post-operative cisplatin chemotherapy and overall survival (P < 0.05).

Conclusion

An elevated APE1/Ref-1 level might serve as a novel potential diagnostic biomarker for OSCC and it can reflect the treatment response to cisplatin chemotherapy and prognosis.

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