Tim-3、CYFRA21-1、SAMHD1在食管癌中的表达及诊断预后价值

Expression and prognostic value of Tim-3, CYFRA21-1 and SAMHD1 in esophageal cancer

目的 探析食管癌患者的T细胞免疫球蛋白黏蛋白-3(Tim-3)、细胞角蛋白19片段抗原21-1(CYFRA21-1)、组氨酸/天冬氨酸残基双联体结构域包涵蛋白1(SAMHD1)水平表达及在疾病诊断中的临床意义、预后价值。方法 选择2019年1月至2021年3月收治的102例食管癌患者(观察组)、同期88例健康体检者(对照组)作为研究对象。采用实时荧光定量聚合酶链反应(RT-PCR)法、全自动化学发光免疫分析仪测定Tim-3、CYFRA21-1、SAMHD1的表达水平,绘制受试者工作特征(ROC)曲线分析3项指标联合检测在食管癌诊断及病理分期诊断中的应用价值,应用logistic回归分析法探析Tim-3、CYFRA21-1、SAMHD1与食管癌预后的关系。结果 观察组治疗前的Tim-3、CYFRA21-1检测值均高于对照组,SAMHD1检测值低于对照组,差异有统计学意义(P<0.05)。观察组治疗后6个月的Tim-3、CYFRA21-1检测值低于治疗前、治疗后1个月,SAMHD1检测值高于治疗前、治疗后1个月(P<0.05),差异有统计学意义(P<0.05)。Tim-3水平与CYFRA21-1呈正相关,与SAMHD1呈负相关;CYFRA21-1与SAMHD1呈负相关(P<0.05)。绘制ROC曲线,结果显示,Tim-3、CYFRA21-1、SAMHD1联合检测在食管癌诊断中的AUC(0.855,95%CI=0.705~0.899)最大,敏感度、特异度分别为95.10%、90.91%(P<0.05)。晚期食管癌患者的Tim-3、CYFRA21-1检测值高于早期、中期患者,晚期食管癌患者的SAMHD1检测值低于早期、中期患者,差异有统计学意义(P<0.05)。三项指标联合检测在食管癌病理分期诊断中的AUC(0.818,95%CI=0.701~0.878)最大,敏感度、特异度分别为93.02%、89.83%(P<0.05)。预后良好者的Tim-3、CYFRA21-1检测值低于预后不良者,预后良好者的SAMHD1检测值高于预后不良者,差异有统计学意义(P<0.05)。Logistic回归分析结果显示,Tim-3、CYFRA21-1高表达为食管癌预后不良的影响因素,SAMHD1低表达是食管癌预后不良的影响因素(P<0.05)。结论 Tim-3、CYFRA21-1在食管癌中呈高表达状态,SAMHD1在食管癌中呈低表达状态,此三项指标联合检测能够提升食管癌早期诊断效能,在病理分期及预后评估中具有一定优势,值得推广应用。

Objective To investigate the expression levels of T-cell immunoglobulin mucin-3(Tim-3),cytokeratin 19 fragment antigen 21-1(CYFRA21-1),and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1(SAMHD1)in patients with esophageal cancer and their prognostic significance.Methods From January 2019 to March 2021,102 patients with esophageal cancer(observation group)and 88 healthy subjects(control group)during the same period were selected.The expression levels of Tim-3,CYFRA21-1 and SAMHD1 were measured by real-time quantitative polymerase chain reaction(RT-PCR)and automatic chemiluminescence immunoassay.And receiver operating characteristic(ROC)curves were drawn to analyze the three indicators in predicting the prognosis and pathological staging of esophageal cancer.The correlations of Tim-3,CYFRA21-1,SAMHD1 with prognosis of esophageal cancer was analyzed by logistic regression analysis.Results The Tim-3 and CYFRA21-1 in the observation group before treatment were significantly higher than those in the control group,and SAMHD1 was significantly lower than that in the control group(P<0.05).The values of Tim-3 and CYFRA21-1 in the observation group 6 months after treatment were significantly lower than those before treatment and 1 month after treatment(P<0.05),the value of SAMHD1 was significantly higher than those before treatment and 1 month after treatment(P<0.05).Tim-3 levels were positively correlated with CYFRA21-1 and negatively correlated with SAMHD1(P<0.05);while CYFRA21-1 was negatively correlated with SAMHD1(P<0.05).The ROC curve showed that the combination of Tim-3,CYFRA21-1,and SAMHD1 detection had the largest AUC(0.855,95%CI=0.705~0.899)in the diagnosis of esophageal cancer,and the sensitivity and specificity were 95.10%and 90.91%,respectively(P<0.05).The values of Tim-3 and CYFRA21-1 in patients with advanced esophageal cancer were significantly higher than those in patients with early and middle stage,and the value of SAMHD1 in patients with advanced esophageal cancer was significantly lower than those in patients with early and middle stage.The combination of Tim-3,CYFRA21-1,and SAMHD1 detection had the largest AUC(0.818,95%CI=0.701~0.878)in staging of esophageal cancer,and the sensitivity and specificity were 93.02%and 89.83%,respectively(P<0.05).The values of Tim-3 and CYFRA21-1 in patients with good prognosis were significantly lower than those in patients with poor prognosis,and the value of SAMHD1 in patients with good prognosis was significantly higher than that in patients with poor prognosis.Logistic regression analysis showed that high expression of Tim-3 and CYFRA21-1 was associated with poor prognosis of esophageal cancer,and so was low expression of SAMHD1(P<0.05).Conclusion Tim-3 and CYFRA21-1 are up-regulated in esophageal cancer,while SAMHD1 is down-regulated.The combined detection of these three indicators can improve the efficiency of early diagnosis of esophageal cancer,and has certain advantages in pathological staging and prognosis evaluation.