外周血BUB1B和KIF11预测非肌层浸润性膀胱癌患者经尿道膀胱肿瘤电切术后复发的价值

Values of BUB1B and KIF11 in peripheral blood in predicting recurrence after transurethral resection of bladder tumor for patients with non-muscle-invasive bladder cancer

  • 摘要:
    目的 探讨外周血BUB1有丝分裂检查点丝氨酸/苏氨酸激酶B(BUB1B)和驱动蛋白家族成员11(KIF11)表达水平与经尿道膀胱肿瘤电切术(TURBT)治疗的非肌层浸润性膀胱癌(NMIBC)患者术后复发的关系。
    方法 采用回顾性病例对照研究设计,选取2019年1月—2021年12月在陕西省核工业二一五医院首次就诊的188例行标准TURBT治疗的NMIBC患者作为研究对象。随访36个月,依据病理检查结果将患者分为复发组(n=68)和未复发组(n=120)。另选取同期健康体检者50例作为对照组。比较复发组、未复发组与对照组外周血BUB1B mRNA和KIF11 mRNA水平; 比较复发组与未复发组临床资料; 采用Cox比例风险回归模型对接受TURBT的NMIBC患者的术后随访数据进行分析; 绘制Kaplan-Meier图进行Cox模型比例风险假定(PH假定)。采用受试者工作特征(ROC)曲线评估各项指标对NMIBC患者术后复发的预测效能。
    结果 对照组、未复发组、复发组外周血BUB1B mRNA和KIF11 mRNA水平依次升高,差异有统计学意义(P < 0.001)。复发组病理T1分期、多发肿瘤患者数多于未复发组,差异有统计学意义(P < 0.05)。2组肿瘤数目、病理分期、BUB1B mRNA和KIF11 mRNA水平与复发率的Kaplan-Meier曲线关系图基本平行,可以认为满足PH假定。多发肿瘤、病理T1分期、BUB1B mRNA及KIF11 mRNA水平是NMIBC患者TURBT治疗后复发的独立影响因素(P < 0.05)。ROC曲线分析结果显示,多发肿瘤、病理T1分期、BUB1B mRNA及KIF11 mRNA水平预测NMIBC患者术后复发的曲线下面积(AUC)分别为0.674、0.746、0.610、0.642, 上述指标联合预测的AUC为0.826(95%CI: 0.767~0.884), 敏感度为86.80%, 特异度为75.30%, 预测效能较好。
    结论 外周血BUB1B mRNA和KIF11 mRNA水平升高与NMIBC患者TURBT术后复发显著相关,是术后复发的独立危险因素。外周血BUB1B mRNA和KIF11 mRNA作为非侵入性生物标志物,可联合临床参数显著提高术后复发预测效能,为个体化监测提供新策略。

     

    Abstract:
    Objective To investigate the relationships of the expression levels of BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) and kinesin family member 11 (KIF11) in peripheral blood with postoperative recurrence in non-muscle-invasive bladder cancer (NMIBC) patients treated with transurethral resection of bladder tumor (TURBT).
    Methods A retrospective case-control study design was employed. A total of 188 NMIBC patients who received standard TURBT treatment in the 215th Hospital of Shaanxi Nuclear Industry during initial visit from January 2019 to December 2021 were selected as research objects. Patients were followed up for 36 months and divided into recurrence group (n=68) and non-recurrence group (n=120) based on pathological examination results. Additionally, 50 healthy individuals who underwent physical examinations during the same period were selected as control group. The levels of BUB1B mRNA and KIF11 mRNA in peripheral blood were compared among the recurrence group, non-recurrence group, and control group. Clinical data were compared between the recurrence and non-recurrence groups. Cox proportional hazards regression models were used to analyze the postoperative follow-up data of NMIBC patients with TURBT. Kaplan-Meier plots were drawn to assess the proportional hazards assumption (PH assumption)of the Cox model. The predictive efficacy of various indicators for postoperative recurrence in NMIBC patients was evaluated using receiver operating characteristic (ROC) curve.
    Results The levels of BUB1B mRNA and KIF11 mRNA in peripheral blood in the control group, non-recurrence group, and recurrence group sucessively increased (P < 0.001). The recurrence group had a significantly higher number of patients with pathological T1 staging and multiple tumors compared to the non-recurrence group (P < 0.05). The Kaplan-Meier curves for the number of tumors, pathological staging, BUB1B mRNA, and KIF11 mRNA levels were generally parallel to recurrence rates between the two groups, meeting PH assumption. Multiple tumors, pathological T1 staging, BUB1B mRNA, and KIF11 mRNA levels were independent influencing factors for recurrence in NMIBC patients after TURBT treatment (P < 0.05). ROC curve analysis showed that the areas under the curves (AUCs) for predicting postoperative recurrence in NMIBC patients by multiple tumors, pathological T1 staging, BUB1B mRNA, and KIF11 mRNA levels were 0.674, 0.746, 0.610 and 0.642, respectively. The combined prediction using these indicators yielded an AUC of 0.826 (95%CI, 0.767 to 0.884), with a sensitivity of 86.80% and a specificity of 75.30%, indicating good predictive efficacy.
    Conclusion Elevated levels of BUB1B mRNA and KIF11 mRNA in peripheral blood are significantly associated with postoperative recurrence in NMIBC patients after TURBT and serve as independent risk factors for recurrence. As non-invasive biomarkers, BUB1B mRNA and KIF11 mRNA in peripheral blood combined with clinical parameters can significantly improve the predictive efficacy of postoperative recurrence, providing a new strategy for individualized monitoring.

     

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