鼻颅底肿瘤SALL4,MAGE-A3特异性CTL免疫反应水平及其临床意义

Specific CTL immune response levels of SALL4 and MAGE-A3 in nasal and skull base tumors and their clinical significance

目的:探讨鼻颅底肿瘤人类婆罗双树样基因-4(SALL4)和黑色素瘤抗原-A3(MAGE-A3)特异性CTL免疫反应水平及其临床意义。方法:收集2016年5月至2017年12月期间在南阳市中心医院经病理学确诊的鼻颅底肿瘤患者62例作为研究对象。统计所有入选对象血清SALL4,MAGE-A3特异性CTL免疫反应水平数据,分析血清SALL4,MAGE-A3特异性CTL免疫反应频率及强度与患者临床病理参数的关系。以患者4~18个月的随访结果进行分组,将随访期间出现肿瘤复发、转移或死亡等任意一项的患者纳入不良组,其余纳入良好组。绘制ROC曲线分析血清SALL4,MAGE-A3特异性CTL免疫反应水平预测患者预后的效能。结果:鼻颅底肿瘤患者血清中SALL4,MAGE-A3特异性CTL免疫反应频率分别为58.06%(36/62),54.84%(34/62),反应强度分别为4 089.26±263.76 SFC/106 PBMC,2 389.17±167.53 SFC/106 PBMC。血清SALL4,MAGE-A3特异性CTL免疫反应频率及强度在患者的分化程度、肿瘤大小、肿瘤侵袭性之间比较,差异无统计学意义(P>0.05),在TNM分期I^II期与III^IV期的对比,差异有统计学意义(P<0.05)。为期4~18个随访统计,预后不良者30例(48.39%),预后良好者32例(51.61%)。通过ROC曲线分析及最大约登指数计算出血清SALL4,MAGE-A3特异性CTL免疫反应频率及强度的AUC面积为SALL4(0.853),MAGE-A3(0.765)。以最大约登指数计算得出SALL4,MAGE-A3指标的最大AUC面积相应参数截止值,其中SALL4截止值为3 789.178 SFC/10~6 PBMC(灵敏度=81.70%,特异性=92.60%),MAGE-A3截止值为2 342.275 SFC/10~6 PBMC(灵敏度=77.40%,特异性=81.30%)。结论:鼻颅底肿瘤SALL4,MAGE-A3特异性CTL免疫反应频率及强度与患者TNM分期密切相关,在预测患者预后方面具有较强的特异性和灵敏度。鼻颅底肿瘤患者血清SALL4,MAGE-A3免疫反应水平对预后诊断具有指导价值。

Objective:To investigate the levels of specific CTL immune response of SALL4 and MAGE-A3 in nasal and skull base tumors and clinical significance.Methods:Sixty-two patients with nasal and skull base tumors confirmed by pathology in our hospital from May 2016 to December 2017 were collected as subjects.Statistical data of serum SALL4 and MAGE-A3 specific CTL immune response levels were collected,and the relationship between serum SALL4 and MAGE-A3 specific CTL immune response frequency and intensity and clinicopathological parameters was analyzed.The patients were followed up for 4 to 18 months,and the prognosis was grouped.The patients who had recurrence,metastasis or death during the follow-up period were included in the poor group and the others in the good group.The ROC curve was drawn to analyze the efficacy of serum SALL4 and MAGE-A3 specific CTL immune response levels in predicting the prognosis of patients.Results:The specific CTL immune response frequencies of SALL4 and MAGE-A3 were 58.06%(36/62) and 54.84%(34/62),respectively.The response intensity of SALL4 and MAGE-A3 were(4 089.26±263.76) SFC/10~6 PBMC and(2 389.17±167.53) SFC/10~6 PBMC,respectively.There was no significant difference in the frequency and intensity of serum SALL4 and MAGE-A3 specific CTL immune response between the degree of differentiation,the size of tumors and the invasiveness of tumors(P>0.05).There was a significant difference between I–II and III–IV stages of TNM(P<0.05).During the follow-up period of 4 to 18 years,there were 30 patients with poor prognosis(poor group),accounting for 48.39%(30/62),32 patients with good prognosis(good group),accounting for 51.61%(32/62).Through ROC curve analysis and maximum Yoden index,the AUC area of serum SALL4 and MAGE-A3 specific CTL immune response frequency and intensity were calculated as SALL4(0.853) and MAGE-A3(0.765).The cut-off values of the maximum AUC area of SALL4 and MAGE-A3 were calculated by the maximum Yoden index.The cut-off values of SALL4 and MAGE-A3 were 3 789.178 SFC/10~6 PBMC(sensitivity =81.70%,specificity =92.60%) and 2 342.275 SFC/10~6 PBMC(sensitivity =77.40%,specificity =81.30%).Conclusion:The frequency and intensity of SALL4 and MAGE-A3 specific CTL immune response in nasal and skull base tumors are closely related to TNM staging,and have strong specificity and sensitivity in predicting the prognosis of patients.Detection of serum levels of SALL4 and MAGE-A3 in patients with nasal and skull base tumors can provide guidance for prognosis diagnosis.