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| 尿液miR-30a-5p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 urine miR-30a-5p for neoadjuvant chemotherapy response and prognosis in patients with muscular invasive bladder cancer |
| 投稿时间：2024-10-21 修订日期：2025-01-02 |
| DOI： |
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| 中文关键词: miR-30a-5p 肌层浸润性膀胱癌 新辅助化疗 肿瘤进展 |
| 英文关键词:miR-30a-5p muscle-invasive bladder cancer neoadjuvant chemotherapy tumor progression |
| 基金项目:咸阳市重点研发计划(S2022-ZDYF-SF-1062) |
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| 摘要点击次数: 36 |
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| 中文摘要: |
| 目的 探讨尿液微小RNA(miR)-30a-5p与肌层浸润性膀胱癌(MIBC)患者新辅助化疗(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月在我院泌尿外科接受NAC和根治性膀胱切除术(RC)治疗的91例MIBC患者的临床资料。根据患者治疗反应分为化疗敏感组和化疗抵抗组。采用实时荧光定量PCR(qRT-PCR)检测尿miR-30a-5p表达水平,定量甲基化特异性聚合酶链反应(qMSP)评估miR-30a-5p启动子区甲基化状态。随访记录患者的总生存期(OS)和疾病特异性生存期(DSS)。结果 根据尿液miR-30a-5p表达中位值(0.72)将MIBC患者分为高表达组(P＞0.72)和低表达组(P≤0.72),低表达组患者淋巴结转移率(P=0.039)及Ki-67指数(P＜0.001)较高表达组更高,且NAC化疗抵抗率更高(P=0.014)。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]。当尿液miR-30a-5p表达≤0.657时,预测NAC化疗反应的受试者工作特征曲线下面积(0.792)和灵敏度(92.60%)较高。Kaplan-Meier生存曲线分析结果显示,尿miR-30a-5p低表达组患者DSS(log-rank=10.054,P=0.002)和OS(log-rank=12.136,P＜0.001)明显短于高表达组患者。单变量和多变量Cox回归分析结果显示,尿液miR-30a-5p是独立影响DSS和OS预后的独立预测因子(P＜0.05)。此外,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关系(Spearman r=-0.7591,P＜0.001)。结论 尿液miR-30a-5p低表达与MIBC患者NAC治疗反应和预后不良有关,可作为MIBC预后和NAC反应预测的可靠生物标志物。 |
| 英文摘要: |
| Objective To investigate the correlation between urinary minor RNA (miR)-30a-5p and neoadjuvant chemotherapy (NAC) response and prognosis in patients with muscule-invasive bladder cancer (MIBC). Methods Retrospective analysis the clinical data of 91 patients with MIBC who received NAC and radical cystectomy (RC) in the Department of Urology in Our hospital from November 2017 to November 2020. Solid Tumor response Assessment Criteria (RECIST) were used to assess patients" response to treatment, and patients were divided into chemotherapy sensitive and chemotherapy resistant groups based on treatment response. Real-time quantitative fluorescent PCR (qRT-PCR) was used to detect the expression level of urinary miR-30a-5p, and to analyze the relationship between the expression level of miR-30a-5p in urine and different clinical characteristics of MIBC patients. Quantitative methylation-specific PCR (qMSP) was used to detect the methylation state of miR-30a-5p promoter region. Overall survival (OS) and disease-specific survival (DSS) were recorded and analyzed. Results MIBC patients were divided into high expression group (P＞0.72) and low expression group (P≤0.72) according to the median value of 0.72 of urinary miR-30a-5p. Compared with the high expression group, the 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=0.014). The expression level of urinary miR-30a-5p in chemotherapy resistant patients 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). When the urinary miR-30a-5p≤0.657, the area under the receiver operating characteristic curve (0.792) and sensitivity (92.60%) for predicting the NAC chemotherapy response were higher. Kaplan-Meier survival curve analysis showed that DSS (log-rank=10.054, P=0.002) and OS (log-rank=12.136, P＜0.001) of patients with low expression of urinary miR-30a-5p were significantly shorter than those of patients with high expression. Univariate and multivariate Cox regression analysis showed that urinary miR-30a-5p was the independent predictor of DSS or OS (P＜0.05). In addition, 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 tissue samples (Spearman r=-0.7591,P＜0.001). Conclusion Low expression of urine miR-30a-5p is associated with poor NAC response and prognosis in MIBC patients, and can be used as a reliable biomarker for predicting MIBC prognosis and NAC response. |
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