食管鳞状细胞癌患者程序性死亡受体配体1表达及其与放疗敏感性及预后的关系

Expression of programmed death-1 ligand-1 in esophageal squamous cell carcinoma and its effect on radiosensitivity and prognosis

目的探讨食管鳞状细胞癌（ESCC）组织中程序性死亡受体配体1（PD-L1）的表达与临床病理特征、放疗敏感性以及预后之间的关系。方法以2012年6月至2015年12月经川北医学院附属医院病理科确诊并完成根治性放疗的90例ESCC患者为研究对象，以20例正常食管黏膜组织作对照。采用免疫组织化学SP法检测PD-L1表达情况。结果PD-L1在ESCC组织中的阳性表达率高于正常食管黏膜[56.7%（51/90）和15.0%（3/20），χ^2=11.367，P〈0.05]。PD-L1表达与患者年龄、性别、肿瘤最大直径、病变长度、周围组织侵犯、临床分期及原发肿瘤体积均无关（均P〉0.05），与淋巴结转移有关（χ^2=4.404，P=0.036）。放疗敏感组PD-L1阳性表达率[63.2%（43/68）]高于放疗抗拒组[39%（8/22）]（χ2=4.888，P〈0.05）。单因素分析结果显示，肿瘤最大直径、放疗敏感性GTV-T与ESCC患者PFS（χ^2=6.239，P=0.013；χ2=6.852，P=0.008；χ^2=6.312，P=0.012）、总生存（OS）（χ^2=8.170，P=0.004；χ^2=4.261，P=0.039；χ2=5.003，P=0.025）有关。多因素分析结果显示，放疗敏感性影响ESCC患者PFS（OR=0.512，95% CI 0.275-0.954，P=0.035）；肿瘤最大直径影响ESCC患者的OS（OR=0.507，95% CI 0.266-0.968，P=0.039）。结论PD-L1在ESCC组织中表达高于正常食管黏膜组织。PD-L1不能作为预测食管癌放疗患者预后的指标，可能作为预测食管癌转移潜能和放疗敏感性的生物标志物。

Objective To investigate the relationship of programmed death ligand-1 （PD-L1） with clinicopathological characteristics, radiosensitivity and prognosis of the patients with esophageal squamous cell carcinoma （ESCC）.Methods Ninety ESCC patients who received radical radiotherapy diagnosed by ESCC in Affiliated Hospital of North Sichuan Medical College were enrolled. Twenty cases of normal esophageal mucosa were used as the controls. The expression of PD-L1 was detected by using immunohistochemical SP method.Results The expression of PD-L1 protein was not correlated with age, gender, the maximum diameter of tumor, the length of lesion, the local aggressive of tumor, clinical stage and primary tumor volume （all P 〉 0.05）. However, it was statistically correlated with the lymphatic metastasis （χ^2= 4.404, P= 0.036）. Meanwhile, PD-L1 positive expression was sensitive to radiation （χ^2= 4.888, P 〈 0.05）. Single factor analysis showed that the maximum diameter of tumor and radiosensitivity were correlated with progression-free survival （PFS） （χ^2= 6.239, P= 0.013; χ^2= 6.852, P= 0.008; χ^2= 6.312, P= 0.012） and overall survival （OS） （χ^2= 8.170, P=0.004; χ^2= 4.261, P= 0.039; χ^2= 5.003, P= 0.025） of ESCC patients. Multifactor analysis showed that the radiosensitivity and the maximum diameter of tumor affected PFS （OR= 0.512, 95% CI 0.275-0.954, P= 0.035） and OS （OR= 0.507, 95% CI 0.266-0.968, P= 0.039） in ESCC patients, respectively.Conclusions The level of PD-L1 expression is increased significantly in ESCC tissues compared with the normal esophageal mucosa tissues. PD-L1 may be a novel biomarker for predicting metastatic potential and radiosensitivity in ESCC patients, rather than the prognosis predictors of ESCC patients treated by radiotherapy.