外周血Tim-3表达水平与食管癌放化疗敏感性的相关性研究

The Correlation Between Expression of Tim-3 in Peripheral Blood and Chemoradiotherapy Sensitivity of Esophageal Carcinoma

目的:研究T细胞免疫球蛋白黏蛋白3(Tim-3)表达水平与食管癌(EC)放化疗敏感性的相关性。方法:所有研究对象为2017年1月到2019年12月期间就诊我院的首次确诊EC患者,收集其病理标本及病理资料。采用免疫组化法检测Tim-3蛋白在EC组织和癌旁组织标本的表达,流式细胞技术检测外周血Tim-3水平。比较癌旁组织和EC组织中Tim-3蛋白表达情况,并分析其与EC病理相关参数间的关系;绘制Kaplan-Meier生存曲线进一步评估Tim-3蛋白表达与患者总生存时间(OS)及无病生存时间(DFS)的关系;通过COX多因素回归分析EC预后与Tim-3蛋白表达的关系;绘制Tim-3对EC预后的ROC曲线,并计算曲线下面积(AUC)。结果:经同步放化疗后,所有患者分为敏感组(36例)和抗拒组(42例)。Tim-3在EC组织中高表达(85.90%),而癌旁组织中轻度表达为(10.26%),差异具有统计学意义(P<0.05)。EC组织中Tim-3的异常表达在浸润深度、淋巴结转移及TNM分期具有显著差异(P<0.05),且高表达的Tim-3的患者具有更低的OS及DFS(P<0.05)。COX回归分析可知,Tim-3高表达(HR=4.253,95%CI 1.464-12.353)是影响EC患者放化疗敏感性的独立危险因素。ROC曲线下面积为0.848,预测的灵敏度为86.2%,特异度为76.3%。结论:Tim-3蛋白在放化疗抗拒EC患者癌症组织及血清中高表达,与EC放化疗敏感性存在一定的相关性,可作为预测EC的特异性标志物。

Objective:To investigate the correlation between the expression of T cell immunoglobulin mucin 3(Tim-3)and chemoradiotherapy sensitivity of esophageal carcinoma(EC).Methods:Patients who admitted our hospital from January 2017 to December 2019 were diagnosed EC,and their pathological specimens and pathological data were collected.Immunohistochemistry was used to detect the expression of Tim-3 protein in EC tissues and adjacent tissues.Flow cytometry was used to detect the level of Tim-3 in peripheral blood.The relationship between the expression of Tim-3 protein and the pathological parameters of EC was analyzed.The Kaplan Meier survival curve was plotted to further evaluate the relationship between expression of Tim-3 protein and overall survival(OS)and disease-free survival(DFS).The relationship between the prognosis of EC and the expression of Tim-3 protein was analyzed by COX regression analysis.The ROC curve of Tim-3 on the prognosis of EC was plotted,and the area under the curve(AUC)was calculated.Results:After concurrent chemoradiotherapy,patients were divided into sensitive group(36 cases)and resistance group(42 cases).The expression of Tim-3 was high in EC tissues(85.90%),while it was slightly expressed in paracancerous tissues(10.26%).The difference was statistically significant(P<0.05).The abnormal expression of Tim-3 in EC was significantly different in depth of invasion,lymph node metastasis and TNM stage(P<0.05),and patients with high expression of Tim-3 had lower OS and DFS(P<0.05).COX regression analysis showed that high expression of Tim-3(HR=4.253,95%CI 1.464-12.353)was an independent risk factor for chemoradiotherapy sensitivity in EC patients.The area under ROC curve was 0.848,the sensitivity and specificity of prediction were 86.2%and 76.3%,respectively.Conclusion:Tim-3 protein is highly expressed in cancer tissues and serum of EC patients resistant to radiotherapy and chemotherapy,which has a certain correlation with the sensitivity of EC to radiotherapy and chemotherapy,and can be used as a specific marker to predict EC.