非肌层浸润性膀胱癌患者术后免疫抑制与复发的相关性研究

Correlation between postoperative immunosuppression and recurrence in patients with non-muscle invasive bladder cancer

目的分析非肌层浸润性膀胱癌患者术后免疫抑制与复发的相关性研究。方法选取2015年1月至2019年1月宁波市北仑区人民医院诊治的238例行经尿道膀胱肿瘤切除术的非肌层浸润性膀胱癌患者作为研究对象。术后1周均检测外周血骨髓来源抑制细胞(MDSC)、表达Tie2的单核细胞(TEMs)、血清白细胞介素(IL)-17A和IL-22水平;随访6个月~54个月,根据是否复发,分为复发组(n=96)和未复发组(n=142),比较两组患者临床与病理特征、外周血MDSC、TEMs水平和血清(IL-17A、IL-22)水平,采用Cox比例风险模型进行多因素分析,通过受试者工作特征(ROC)曲线分析上述检测指标预测术后复发的效能及计算最佳截断值,绘制Kaplan-Meier法术后复发曲线,使用Log-Rank检验不同免疫指标高低两组术后复发率的差异性。结果所有患者均获得随访,中位随访时间为24个月,术后复发96例。两组患者外周血MDSC、TEMs水平和血清(IL-17A、IL-22)水平比较,差异均具有统计学意义(均P<0.05);经Cox比例风险模型进行多因素分析,MDSC、TEMs、IL-17A、IL-22水平均是影响术后复发的独立危险因素,差异均具有统计学意义(均P<0.05);经ROC曲线分析,MDSC、TEMs、血清(IL-17A、IL-22)水平预测术后复发的ROC曲线下面积(AUC)分别为0.785、0.795、0.870和0.765,最佳截断值分别为12.45%、15.15%、12.77pg/mL和85.54pg/mL;不同MDSC和TEMs比例,IL-17A、IL-22水平患者术后2年复发率比较,经Log-Rank检验,差异均具有统计学意义(均P<0.05)。结论非肌层浸润性膀胱癌患者术后免疫抑制与复发存在相关关系,MDSC、TEMs、血清(IL-17A、IL-22)水平均是影响术后复发的独立危险因素,具有预测术后复发的潜在效能,在临床上应引起重视。

Objective To analyze the correlation between postoperative immunosuppression and recurrence in patients with non-muscle invasive bladder cancer.Methods 238 patients with non-muscle invasive bladder cancer who underwent transurethral resection of bladder tumor in our hospital from January 2015 to January 2019 were enrolled in the study.The peripheral blood marrow-derived suppressor cells(MDSC),Tie2-expressing monocytes(TEMs),serum interleukin(IL)-17 A and IL-22 levels were measured at a week after surgery.All the patients were followed up for 6 to 54 months and were divided into recurrent group and non-recurrent group.The clinic and pathological features,peripheral blood MDSC,TEMs levels and serum IL-17 A and IL-22 levels were compared between the two groups.The Cox proportional hazard model was used for multivariate analysis;the receiver operating characteristic(ROC)curve was used to analyze the efficacy of the above-mentioned test indicators to predict postoperative recurrence and calculate the optimal cut-off value;the Kaplan-Meier recurrence curve was drawn and Log-Rank test was performed for the difference in the recurrence rate between the two groups of different immune indicators.Results All the patients were followed up,a median follow-up of 24 months and 96 patients had recurrence.The levels of MDSC,TEMs and serum IL-17 A and IL-22 in the two groups were significantly different(all P<0.05).Multivariate analysis was performed by Cox proportional hazard model and found that MDSC,TEMs,IL-17 A and IL-22 were independent risk factors for postoperative recurrence(all P<0.05).According to ROC curve analysis,the AUC predicted by MDSC,TEMs,il-17 a and il-22 was 0.785,0.795,0.870 and 0.765,respectively,and the optimal cut-off values were 12.45%,15.15%,12.77 pg/mL and 85.54 pg/mL.According to the Log-Rank test,there were statistically significant differences in the 2-year postoperative recurrence rate between patients with different MDSC and TEMs,IL-17 A and IL-22 levels(all P<0.05).Conclusions Postoperative immunosuppression is associated with recurrence in patients with non-muscular invasive bladder cancer.MDSC,TEMs,IL-17 A and IL-22 are independent risk factors for postoperative recurrence,with potential efficacy in predicting postoperative recurrence,which should be paid attention to clinically.