Department of Urology, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
J Urol. 2012 Apr;187(4):1466-72. doi: 10.1016/j.juro.2011.11.082. Epub 2012 Feb 17.
Abnormal miRNA expression is associated with prostate cancer progression. However, the relationship between miRNA and biochemical recurrence after radical prostatectomy is not well established. Thus, we evaluated the miRNA miR-21 as a biomarker to predict the risk of biochemical failure, and as a potential drug target for prostate cancer therapy.
miR-21 levels were assayed using locked nucleic acid in situ hybridization coupled with tissue microarray techniques in 169 radical prostatectomy tissue samples. The Cox proportional hazard model was used to analyze miR-21 expression as an independent predictor of biochemical recurrence. The association of miR-21 with recurrence was estimated using the Kaplan-Meier method. miR-21 was also evaluated as a potential drug target for prostate cancer therapy.
miR-21 expression in prostate cancer tissue samples was significantly associated with pathological stage, lymph node metastasis, capsular invasion, organ confined disease, Gleason score, biochemical recurrence and patient followup. Multivariate analysis also indicated that miR-21 expression could be an independent predictor of biochemical recurrence. The 5-year recurrence-free probability for patients positive vs negative for miR-21 expression was 33.9% vs 44.5%. In vivo treatment with antagomir-21 also repressed the tumor growth of DU145 cells in nude mice.
Positive miR-21 expression was associated with poor biochemical recurrence-free survival and predicted the risk of biochemical recurrence in patients with prostate cancer after radical prostatectomy. Accordingly gene therapy using miR-21 inhibition strategies may prove useful for prostate cancer therapy.
异常的 miRNA 表达与前列腺癌的进展有关。然而，miRNA 与根治性前列腺切除术后生化复发之间的关系尚未得到很好的确定。因此，我们评估了 miRNA miR-21 作为预测生化失败风险的生物标志物，以及作为前列腺癌治疗的潜在药物靶点。
使用锁核酸原位杂交结合组织微阵列技术在 169 例根治性前列腺切除术组织样本中检测 miR-21 水平。Cox 比例风险模型用于分析 miR-21 表达作为生化复发的独立预测因子。使用 Kaplan-Meier 方法估计 miR-21 与复发的关联。还评估了 miR-21 作为前列腺癌治疗的潜在药物靶点。
前列腺癌组织样本中的 miR-21 表达与病理分期、淋巴结转移、包膜侵犯、器官局限疾病、Gleason 评分、生化复发和患者随访显著相关。多变量分析还表明，miR-21 表达可以是生化复发的独立预测因子。miR-21 表达阳性与阴性的患者 5 年无生化复发生存率分别为 33.9%和 44.5%。在体内用 antagomir-21 治疗也抑制了裸鼠中 DU145 细胞的肿瘤生长。
miR-21 表达阳性与生化无复发生存不良相关，并预测了根治性前列腺切除术后前列腺癌患者的生化复发风险。因此，使用 miR-21 抑制策略的基因治疗可能对前列腺癌治疗有用。
