Molecular Pathology Program, Spanish National Cancer Center, Madrid, Spain.
J Urol. 2010 Oct;184(4):1507-13. doi: 10.1016/j.juro.2010.05.085. Epub 2010 Aug 17.
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.
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.
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).
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.
卡介苗是降低高危非肌肉浸润性膀胱癌肿瘤复发和进展的标准治疗方法。然而，目前尚不清楚哪些 T1G3 病例更容易出现侵袭性更强的临床行为，或者更容易对卡介苗产生反应。我们评估了肌联蛋白甲基化作为 T1G3 膀胱癌患者卡介苗反应的临床预后预测因子和预测生物标志物的作用。
我们分析了 170 例 T1G3 膀胱癌患者肿瘤标本中的肌联蛋白甲基化状态，其中包括 108 例接受卡介苗治疗的患者亚组。通过甲基化特异性聚合酶链反应评估肌联蛋白甲基化。使用竞争风险回归分析评估复发、进展为肌肉浸润性肿瘤和疾病特异性总生存。
在分析的 170 例病例中，72 例（42.4%）复发，36 例（21.2%）进展。共有 24 例患者（14.1%）死于该疾病。单变量和多变量生存分析显示，肌联蛋白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率缩短（p = 0.020）显著相关。在接受卡介苗治疗的亚组中，肌联蛋白甲基化也与复发率增加（p = 0.011）、进展（p = 0.030）和疾病特异性总生存率缩短（p = 0.028）相关。
表观遗传学分析显示，肌联蛋白甲基化与 T1G3 疾病患者的肿瘤侵袭性和临床结局相关。肌联蛋白甲基化可区分对卡介苗有反应的患者和可能需要更积极治疗方法的患者。
