Myopodin Methylation is Associated With Clinical Outcome in Patients With T1G3 Bladder Cancer
Myopodin Methylation is Associated With Clinical Outcome in Patients With T1G3 Bladder Cancer
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DOI：
10.1016/j.juro.2010.05.085
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发表时间：
2010-10-01
影响因子：
6.6
通讯作者：
Sanchez-Carbayo, Marta
中科院分区：
文献类型：
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作者：
Alvarez-Mugica, Miguel;Cebrian, Virginia;Sanchez-Carbayo, Marta
目的：卡介苗是一种标准的治疗方法，可减少肿瘤复发，延缓非肌源性膀胱肿瘤的进展。然而，目前尚不清楚哪些T1G3病例更容易出现更具侵略性的临床行为，或对卡介苗芽孢杆菌更敏感。我们评估了myopodin甲基化作为T1G3膀胱肿瘤患者卡介苗应答的临床预后预测和预测性生物标志物的作用。材料和方法：我们分析了170例T1G3膀胱癌患者肿瘤标本中myopodin的甲基化状态，其中包括108例接受卡介苗- guerin治疗的患者。通过甲基化特异性聚合酶链反应评估Myopodin甲基化。使用竞争风险回归分析分析复发、进展为肌肉侵袭性肿瘤和疾病特异性总生存率。结果：170例患者中复发72例（42.4%），进展36例（21.2%）。共有24例（14.1%）患者死于该病。单因素和多因素生存分析显示，myopodin甲基化与复发率增加（p = 0.004）、进展（p = 0.002）和疾病特异性总生存（p = 0.020）显著相关。在用卡介苗- guerin芽孢杆菌治疗的亚组中，myopodin甲基化还与复发率增加（p = 0.011）、进展（p = 0.030）和疾病特异性总生存期缩短（p = 0.028）相关。结论：表观遗传学分析显示，myopodin甲基化与T1G3患者的肿瘤侵袭性和临床结局相关。Myopodin甲基化区分了对卡介苗芽孢杆菌有反应的患者和那些可能需要更积极治疗方法的患者。
Purpose: Bacillus Calmette-Guerin is standard treatment to decrease tumor recurrence and delay progression of high risk, nonmuscle invasive bladder tumors. However, it is not yet clear which T1G3 cases are more prone to more aggressive clinical behavior or susceptible to respond to bacillus Calmette-Guerin. We evaluated the role of myopodin methylation as a clinical outcome prognosticator and predictive biomarker for the bacillus Calmette-Guerin response in patients with T1G3 bladder tumors.Materials and Methods: We analyzed the methylation status of myopodin in tumor specimens from 170 patients with T1G3 bladder cancer, including a subset of 108 who underwent bacillus Calmette-Guerin treatment. Myopodin methylation was assessed by methylation specific polymerase chain reactions. Recurrence, progression to muscle invasive tumors and disease specific overall survival were analyzed using competing risks regression analysis.Results: Of the 170 cases analyzed 72 recurred (42.4%) and 36 progressed (21.2%). A total of 24 patients (14.1%) died of the disease. Univariate and multivariate survival analysis revealed that myopodin methylation was significantly associated with an increased recurrence rate (p = 0.004), progression (p = 0.002) and shorter disease specific overall survival (p = 0.020). In a subset treated with bacillus Calmette-Guerin myopodin methylation was also related to an increased recurrence rate (p = 0.011), progression (p = 0.030) and shorter disease specific overall survival (p = 0.028).Conclusions: Epigenetic analysis revealed that myopodin methylation was associated with tumor aggressiveness and clinical outcome in patients with T1G3 disease. Myopodin methylation distinguished patients responding to bacillus Calmette-Guerin from those who may require a more aggressive therapeutic approach.