Xie Jianli, Li Ying, Kong Jingjing, Li Chong
Attending Doctor, Department of Prosthodontics, Jinan Stomatological Hospital, Jinan, Shandong, People's Republic of China.
Nurse-in-Charge, Department of Liver Disease, Infectious Disease Hospital, Jinan, Shandong, People's Republic of China.
J Oral Maxillofac Surg. 2019 Apr;77(4):859-866. doi: 10.1016/j.joms.2018.11.034. Epub 2018 Dec 11.
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.
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.
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).
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.
脱嘌呤/脱嘧啶内切酶1/氧化还原因子-1（APE1/Ref-1）是一种多功能蛋白，在包括口腔鳞状细胞癌（OSCC）在内的多种癌症中表达升高。然而，此类患者血清APE1/REF-1水平仍不清楚。本研究的目的是评估OSCC患者血清APE/Ref-1水平，并测定其与OSCC诊断、临床病理特征及预后的相关性。
本病例对照研究共纳入98例原发性OSCC患者和109例年龄或性别匹配的正常对照。预测变量为血清APE1/Ref-1水平，采用酶联免疫吸附测定法进行检测。结局变量包括诊断、临床病理特征、治疗反应及OSCC预后。使用X-tile程序以最小P值确定血清APE1/Ref-1的最佳截断点。采用单因素和多因素Cox回归模型评估预后因素。
患者组和对照组的平均年龄分别为51.6±8.7岁（63例男性；35例女性）和52.4±10.3岁（67例男性；42例女性）。OSCC患者血清APE1/Ref-1水平显著高于对照组（4.56±1.09 ng/mL对3.18±0.88 ng/mL；P<0.01）。在TNM分期较晚、有淋巴结转移及病理分化较差的OSCC患者中观察到更高的血清APE1/Ref-1水平。受试者工作特征曲线分析表明，血清APE1/Ref-1水平是区分OSCC的潜在生物标志物，曲线下面积为0.83（95%置信区间，0.78至0.88；敏感性，0.87；特异性，0.68）。对数秩分析显示，OSCC且APE1/Ref-1水平较低的患者在术后顺铂化疗后的无病生存期和总生存期更长（P<0.05）。
APE1/Ref-1水平升高可能是OSCC一种新的潜在诊断生物标志物，可反映对顺铂化疗的治疗反应及预后。
