施 量,陈汉轩,李静凯,等.尿液miR-30a-5p表达对肌层浸润性膀胱癌患者新辅助化疗反应和预后的预测价值[J].肿瘤学杂志,2026,32(1):46-53.
尿液miR-30a-5p表达对肌层浸润性膀胱癌患者新辅助化疗反应和预后的预测价值
Predictive Value of Urinary miR-30a-5p Expression for Neoadjuvant Chemotherapy Response and Prognosis in Patients with Muscular-Invasive Bladder Cancer
投稿时间:2024-10-21  
DOI:10.11735/j.issn.1671-170X.2026.01.B008
中文关键词:  miR-30a-5p  膀胱肿瘤  新辅助化疗  疗效  预后
英文关键词:miR-30a-5p  bladder neoplasms  neoadjuvant chemotherapy  response  prognosis
基金项目:咸阳市重点研发计划(S2022-ZDYF-SF-1062)
作者单位
施 量 咸阳市第一人民医院 
陈汉轩 咸阳市第一人民医院 
李静凯 咸阳市第一人民医院 
任 磊 咸阳市第一人民医院 
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中文摘要:
      摘 要:[目的] 探讨尿液微小RNA(miR)-30a-5p表达与肌层浸润性膀胱癌(muscule-invasive bladder cancer,MIBC)患者新辅助化疗(neoadjuvant chemotherapy,NAC)反应和预后的相关性。[方法] 回顾性分析2017年11月至2020年11月咸阳市第一人民医院收治的91例MIBC患者的临床资料,患者均接受了基于顺铂和吉西他滨的NAC方案,然后行膀胱手术。NAC治疗2个周期后评估肿瘤反应,将患者分为化疗敏感组和化疗抵抗组。采用实时荧光定量PCR检测尿液miR-30a-5p表达水平,定量甲基化特异性聚合酶链反应评估miR-30a-5p启动子区甲基化状态。分析尿液miR-30a-5p表达水平与患者总生存期(overall survival,OS)和疾病特异性生存期(disease specific survival,DSS)的关系。[结果] 根据尿液miR-30a-5p表达中位值(0.72)将MIBC患者分为高表达(>0.72)组和低表达(≤0.72)组,miR-30a-5p低表达组患者淋巴结转移率(P=0.039)及Ki-67指数(P<0.001)较miR-30a-5p高表达组更高,且NAC化疗抵抗率更高(P=0.027)。化疗抵抗患者尿液miR-30a-5p表达水平明显低于化疗敏感组[0.53(0.26,0.94) vs 1.93(0.71,6.32),P=0.014]。尿液miR-30a-5p表达水平(≤0.66)预测NAC化疗敏感性的受试者工作特征曲线下面积(0.792)和灵敏度(92.60%)均较高。多因素分析显示,尿液miR-30a-5p是NAC敏感的独立预测因素(OR=0.323,95%CI:0.132~0.792,P=0.013)。miR-30a-5p低表达组患者中位DSS时间(328.0 d vs 614.5 d,P=0.002)和中位OS时间(495.5 d vs 1 026.0 d,P<0.001)均短于高表达组。尿液miR-30a-5p表达水平和MIBC组织样本中miR-30a-5p启动子CpG岛的甲基化率呈负相关(r=-0.759,P<0.001)。[结论] 尿液miR-30a-5p低表达与MIBC患者NAC治疗反应和不良预后有关,可作为MIBC预后和NAC反应预测的生物标志物。
英文摘要:
      Abstract:[Objective] To investigate the predictive value of urinary microRNA (miR)-30a-5p expression for neoadjuvant chemotherapy(NAC) response and survival prognosis in patients with muscule-invasive bladder cancer (MIBC). [Methods] The clinical data of 91 MIBC patients admitted in First People’s Hospital of Xianyang from November 2017 to November 2020 were retrospectively analyzed. All patients received preoperative NAC regimen based on cisplatin and gemcitabine. According to the evaluation of tumor response after 2 cycles of NAC treatment, patients were divided into chemotherapy sensitive group and chemotherapy resistant group. The expression of urinary miR-30a-5p was detected by real-time quantitative fluorescent PCR (qRT-PCR), the methylation state of miR-30a-5p promoter region was detected by quantitative methylation-specific PCR (qMSP). The relationship of urinary miR-30a-5p expression level with overall survival (OS) and disease specific survival (DSS) was analyzed. [Results] Patients were divided into high expression group(P>0.72) and low expression group(P≤0.72), according to the median value of urinary miR-30a-5p expression. Compared with the miR-30a-5p high expression group, the miR-30a-5p low expression group had a higher lymph node metastasis rate (P=0.039) and Ki-67 index (P<0.001), and had higher chemotherapy resistance rate(P=0.027). The expression level of urinary miR-30a-5p in chemotherapy resistant group was significantly lower than that of chemotherapy sensitive group [0.53 (0.26,0.94) vs 1.93 (0.71,6.32), P=0.014]. The area under the receiver operating characteristic curve of urinary miR-30a-5p for predicting chemotherapy response was 0.792, with a sensitivity of 92.60% (cut-off value=0.66). Multivariate analysis showed that urinary miR-30a-5p was an independent factor affecting NAC sensitivity (OR=0.323, 95%CI: 0.132~0.792, P=0.013). The median DSS time (328.0 d vs 614.50 d, P=0.002) and median OS time (495.5 d vs 1 026.0 d, P<0.001) in the miR-30a-5p low expression group were shorter than those in the high expression group. The expression level of urine miR-30a-5p was negatively correlated with the methylation rate of CpG island of miR-30a-5p promoter in MIBC tissues (r=-0.759, P<0.001). [Conclusion] Low expression of urinary miR-30a-5p is associated with poor NAC response and prognosis in MIBC patients, indicating that it may be used as a biomarker for predicting MIBC prognosis and NAC response.
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