PD-L1和APE1在早期宫颈鳞癌中的表达及临床意义

Expression and clinical significance of APE1 and PD-L1 in early stage cervical squamous cell carcinoma

目的探讨早期宫颈鳞癌组织中程序性死亡配体-1(programmed death ligand-1,PD-L1)和脱嘌呤/脱嘧啶内切核酸酶1(apurinic/apyrimidinic endonuclease1,APE1)的表达与临床特征及预后的关系。方法采用免疫组织化学的方法(IHC)检测PD-L1和APE1蛋白在64例早期宫颈鳞癌组织中的表达,分析PD-L1、APE1表达以及两者共表达与早期宫颈癌临床特征的关系;采用Spearman等级相关分析检测APE1与PD-L1表达的相关性,Kaplan-Meier法分析早期宫颈鳞癌患者中APE1与PD-L1的表达与术后生存的关系,Cox回归模型分析早期宫颈鳞癌患者预后的危险因素。结果早期宫颈癌患者APE1和PD-L1蛋白表达阳性率分别为70.31%和67.18%。PD-L1的表达与分期、淋巴结转移有显著相关性(P<0.05),而APE1的表达仅与淋巴结转移密切相关(P=0.038)。另外,APE1与PD-L1的表达正相关(r2=0.347,P=0.005),且两者共表达与淋巴结转移相关,其术后生存期比单一阳性表达的宫颈癌患者明显缩短(P<0.05)。多因素COX回归模型结果显示,APE1的表达和淋巴结转移是影响早期宫颈鳞癌预后的独立危险因素,危险度分别为16.187(P=0.01)和27.340(P<0.001)。结论PD-L1和APE1表达的联合检测对早期宫颈鳞癌预后评估具有潜在的临床价值。

Objective To determine the expression levels of apurinic/apyrimidinic endonuclease 1 （APE1） and programmed death ligand-1 （PD-L1） in early stage cervical squamous cell carcinoma and explore their clinical significance. Methods Immunohistochemical staining was applied to detect the expression of APE1 and PD-L1 in 64 samples of early stage cervical squamous cell carcinoma. The correlation of their expression with clinicopathological features of the patients with cervical cancer was analyzed. Spearman rank correlation analysis was used to study the correlation between APE1 expression and PD-L1expression, Kaplan-Meier survival analysis to evaluate the impact of APE1 and PD-L1 expression on postoperative survival of the patients, and Cox univariate and multivariate prognostic analysis to explore the prognostic factors of the patients. Results The positive rate of APE1 was 70.31%, and that of PD-L1 was 60.18% in the 64 samples. The expression of PD-L1 was closely correlated with the stage of the International Federation of Gynecology and Obstetrics （FIGO） and lymphatic metastasis （P〈0.05）, and the expression of APE1 expression was closely correlated with lymphatic metastasis （P=0.038）. Spearman rank correlation analysis indicated that the expression of APE1 was positively correlated with that of PDL1 （r2=0.347, P=0.005）, and their co-expression was closely correlated with lymphatic metastasis, and the survival time was obviously shorter in those with co-expression than those with single expression （P〈0.05）. Multivariate Cox analysis revealed that the expression of APE1 and lymphatic metastasis were independent risk factors for the prognosis of the patients with early stage cervical squamous cell carcinoma （Hazard ratio=16.187, P=0.01; Hazard ratio=27.340, P〈0.001）. Conclusion Combinatorial detection of APE1 and PD-L1 is of potential value for the prognosis evaluation of early stage cervical squamous cell carcinoma.