膀胱癌病人血清miR-143-3p、ATG2B水平与临床病理及预后生存的关系

Correlation of serum miR-143-3p and ATG2B levels with clinicopathology and postoperative survival in patients with radical cystectomy

目的探讨miR-143-3p、ATG2B在膀胱癌病人血清中的表达及其与临床病理和病人预后的关系。方法2017年1月~2019年1月在我院进行膀胱癌根治术的病人88例为研究组,本院行健康体检的志愿者80例为对照组。实时荧光定量PCR(qRT-PCR)法检测病人术前、术后4周静脉血miR-143-3p、ATG2B水平;pearson分析二者的相关性。通过受试者工作特征(ROC)曲线评估miR-143-3p、ATG2B对膀胱癌的预测价值。用Kaplan-Meier法绘制生存曲线;通过多因素Cox回归分析膀胱癌根治术病人预后的影响因素。结果miR-143-3p在膀胱癌病人血清中表达水平较对照组降低(0.68±0.12 vs.0.87±0.26),ATG2B表达水平升高(1.02±0.30 vs.0.61±0.18),差异有统计学意义(P<0.05);病人术后血清中miR-143-3p水平较术前升高(0.77±0.23 vs.0.68±0.12),ATG2B水平较术前降低(0.85±0.26 vs.1.02±0.30),差异有统计学意义(P<0.05);研究组miR-143-3p与ATG2B表达呈负相关(r=-0.454,r=-0.407,P<0.01);miR-143-3p对膀胱癌的诊断AUC为0.846(95%CI:0.783~0.897),敏感度、特异度分别为79.55%、78.75%;ATG2B对膀胱癌诊断AUC为0.883(95%CI:0.824~0.927),敏感度、特异度分别为78.41%、81.25%;二者联合诊断膀胱癌的AUC为0.939(95%CI:0.891~0.970),敏感度、特异度分别为87.50%、88.75%。miR-143-3p低表达组3年生存率(34.88%,15/43)低于高表达组(77.78%,35/45),ATG2B高表达组3年生存率(40.91%,18/44)低于低表达组(72.73%,32/44),差异有统计学意义(Log-rankχ^(2)=18.055,8.658,P=0.000,0.003)。多因素Cox回归分析表明,淋巴结转移、远处转移、肿瘤病理分级、TNM分期、miR-143-3p、ATG2B是膀胱癌病人生存状况的影响因素。结论膀胱癌病人血清中miR-143-3p呈低表达,ATG2B呈高表达,二者表达与膀胱癌病人临床病理特征和预后密切相关。

Objective To investigate the expression of miR-143-3p and ATG2B in serum of patients with bladder cancer and their relationship with clinicopathology,prognosis and survival of patients.Methods Eighty-eight patients who underwent radical bladder cancer surgery in our hospital from January 2017 to January 2019 were regarded as the research group,and 80 volunteers who underwent physical examination in our hospital were included as the control group.Quantitative real-time PCR(qRT-PCR)method was performed to detect the levels of miR-143-3p and ATG2B;The predictive value of miR-143-3p and ATG2B for bladder cancer was evaluated by ROC curve.Draw survival curve using Kaplan Meier method;The prognostic factors of bladder cancer patients were analyzed by Cox regression.Results The expression level of miR-143-3p in the serum of bladder cancer patients was lower than that in the control group(0.68±0.12 vs.0.87±0.26),and the expression level of ATG2B was higher(1.02±0.30 vs.0.61±0.18)(P<0.05);the expression level of miR-143-3p in serum of postoperative patients was higher than that before operation(0.77±0.23 vs.0.68±0.12),and the expression level of ATG2B was lower than that before operation(0.85±0.26 vs.1.02±0.30)(P<0.05);The study group showed a negative correlation between miR-143-3p and ATG2B expression(r=-0.454,r=-0.407,P<0.01);The AUC of miR-143-3p in the diagnosis of bladder cancer was 0.846(95%CI:0.783-0.897),the sensitivity and specificity were 79.55%and 78.75%respectively;The AUC of ATG2B in the diagnosis of bladder cancer was 0.883(95%CI:0.824-0.927),the sensitivity and specificity were 78.41%and 81.25%respectively;The AUC for the diagnosis of bladder cancer was 0.939(95%CI:0.891-0.970),the sensitivity and specificity were 87.50%and 88.75%,respectively.The 3-year survival rate of the miR-143-3p low expression group was 34.88%(15/43)lower than that of the high expression group 77.78%(35/45),and the 3-year survival rate of the ATG2B high expression group was 40.91%(18/44)lower than that of the low expression group 72.73%(32/44).The differences were statistically significant(Log rankχ^(2)=18.055,8.658,P=0.000,0.003).Lymph node metastasis,distant metastasis,tumor pathological grade,TNM stage,miR-143-3p,ATG2B are all factors influencing the survival of bladder cancer patients.Conclusion The serum expression of miR-143-3p in patients with bladder cancer is low,and the expression of ATG2B is high,and the expressions of the two are closely related to the clinicopathological characteristics and prognosis of patients with bladder cancer.