Laboratory of Medical Investigation, Urology Department, University of São Paulo Medical School, São Paulo, Brazil.
J Urol. 2011 Mar;185(3):1118-22. doi: 10.1016/j.juro.2010.10.035. Epub 2011 Jan 21.
Abnormal miRNA expression has emerged as crucial factors in carcinogenesis and is important in the comprehension of prostate cancer behavior. We determined the correlation of miRNA expression profiles with prostate cancer progression.
We studied frozen specimens from 49 patients treated for prostate cancer with radical prostatectomy. We intentionally chose 28 men without and 21 with biochemical recurrence, defined as prostate specific antigen greater than 0.2 ng/ml. The expression of 14 miRNAs was determined by quantitative reverse transcriptase-polymerase chain reaction. All radical prostatectomy specimens were studied in toto to determine tumor volume, Gleason score and 2002 TNM pathological stage. Benign prostate tissue from benign prostatic hyperplasia served as a control.
Four miRNAs were related to tumor recurrence. Using the Cox regression test the risk of recurrence was 3.0, 3.3, 2.7 and 3.4 for high levels of miR-100, miR-145, miR-191 and miR-let7c, respectively. When considering statistically significant clinical variables on univariate analysis of biochemical-free survival, prostate specific antigen and tumor volume, results revealed that miR-100 and tumor volume were independently related to tumor recurrence.
A high level of miR-100 is related to biochemical recurrence of localized prostate cancer in patients treated with radical prostatectomy. The role of miR-100 during carcinogenesis must be resolved in future studies to better understand the molecular pathways in which miR-100 is involved. This may open the possibility of using it as a prognostic marker and inspire the development of a target drug.
异常 miRNA 表达已成为致癌作用的关键因素，对于理解前列腺癌的行为具有重要意义。我们确定了 miRNA 表达谱与前列腺癌进展的相关性。
我们研究了 49 例接受根治性前列腺切除术治疗前列腺癌的冷冻标本。我们特意选择了 28 例无生化复发（定义为前列腺特异性抗原>0.2ng/ml）和 21 例有生化复发的患者。通过定量逆转录-聚合酶链反应确定了 14 种 miRNA 的表达。对所有根治性前列腺切除术标本进行了全组织研究，以确定肿瘤体积、Gleason 评分和 2002 年 TNM 病理分期。良性前列腺增生的良性前列腺组织作为对照。
有 4 种 miRNA 与肿瘤复发相关。使用 Cox 回归检验，miR-100、miR-145、miR-191 和 miR-let7c 高表达的复发风险分别为 3.0、3.3、2.7 和 3.4。在对生化无复发生存的单因素分析中考虑到有统计学意义的临床变量时，结果表明 miR-100 和肿瘤体积与肿瘤复发独立相关。
miR-100 高水平与根治性前列腺切除术后局部前列腺癌的生化复发相关。在未来的研究中，必须解决 miR-100 在癌变过程中的作用，以更好地理解 miR-100 所涉及的分子途径。这可能为将其用作预后标志物开辟可能性，并激发靶向药物的开发。
