Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 Could Serve as a Potential Serological Biomarker for the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma.

Objective: 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). However, the serum APE1/REF-1 level remains unknown in such patients. The purpose of the present study was to estimate the serum APE/Ref-1 levels in patients with OSCC and measure its association with the diagnosis, clinicopathologic features, and prognosis of OSCC.

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

Results: The average patient and control age was 51.6 ± 8.7 years (63 men; 35 women) and 52.4 ± 10.3 years (67 men; 42 women), respectively. The serum APE1/Ref-1 level was significantly greater in patients with OSCC than that in the controls (4.56 ± 1.09 ng/mL vs 3.18 ± 0.88 ng/mL; P < .01). Much higher serum APE1/Ref-1 levels were observed in those with OSCC with late TNM stage, lymph node metastases, and worse pathologic differentiation. The receiver operating characteristic curve analysis illustrated that the serum APE1/Ref-1 level was a potential biomarker for differentiating OSCC, with an area under the curve of 0.83 (95% confidence interval, 0.78 to 0.88; sensitivity, 0.87; specificity, 0.68). The log-rank analysis revealed that patients with OSCC and a low APE1/Ref-1 level experienced longer disease-free survival after postoperative cisplatin chemotherapy and overall survival (P < .05).

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