Identification of miR-187 and miR-182 as Biomarkers of Early Diagnosis and Prognosis in Patients with Prostate Cancer Treated with Radical Prostatectomy
Identification of miR-187 and miR-182 as Biomarkers of Early Diagnosis and Prognosis in Patients with Prostate Cancer Treated with Radical Prostatectomy
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DOI：
10.1016/j.juro.2014.01.107
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发表时间：
2014-07-01
影响因子：
6.6
通讯作者：
Antonio Lopez-Guerrero, Jose
中科院分区：
文献类型：
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作者：
Casanova-Salas, Irene;Rubio-Briones, Jose;Antonio Lopez-Guerrero, Jose
目的：miRNAs是负调控靶mRNA基因表达的非编码RNA。miRNA的异常表达与前列腺癌的发病机制有关材料和方法：从10例正常前列腺和50例前列腺癌标本中提取总RNA，采用GeneChip（R）miRNA 2.0芯片进行分析。在中位随访92个月（范围2至189）的273个石蜡包埋的前列腺癌样本的独立队列用于验证定量逆转录酶-聚合酶链反应。结果：选择在正常前列腺组织和前列腺肿瘤组织中差异表达最高的miR-182和187作为进一步验证的指标。miR-187与cT（p = 0.125）和pT（p = 0.0002）分期、Gleason评分（p = 0.003）和TMPRSS 2-ERG状态（p = 0.003）呈负相关。对数秩检验显示miR-182与生化（p = 0.026）和临床（p = 0.043）无进展生存期相关，多变量分析也显示了这一点。通过将miR-182表达与Gleason评分相结合，实现了进展风险定义的显著独立改善（p < 0.0001）。尿液中的miR-187检测为阳性活检提供了独立的预测值。包括血清前列腺特异性抗原、尿PCA 3和miR-187的预测模型提供了88.6%的灵敏度和50%的特异性（AUC 0.711，p = 0.001）。结论：结果显示，miR-182和187是前列腺癌预后的有希望的生物标志物，以识别处于进展风险的患者，并用于诊断以提高现有生物标志物的预测能力。
Purpose: miRNAs are noncoding RNAs that negatively regulate target mRNA gene expression. Aberrant miRNA expression is associated with prostate cancer pathogenesis. We identified miRNAs as potential biomarkers for prostate cancer diagnosis and prognosis.Materials and Methods: Total RNA was obtained from 10 normal prostate and 50 prostate cancer samples, and analyzed using the GeneChip (R) miRNA 2.0 Array. At a median followup of 92 months (range 2 to 189) an independent cohort of 273 paraffin embedded prostate cancer samples was used for validation by quantitative reverse transcriptase-polymerase chain reaction. Another 92 urine samples from patients undergoing prostate biopsy were evaluated for these miRNAs.Results: miR-182 and 187, the miRNAs most differentially expressed between normal and tumor tissue, were selected for further validation. miR-187 inversely correlated with cT (p = 0.125) and pT (p = 0.0002) stages, Gleason score (p = 0.003) and TMPRSS2-ERG status (p = 0.003). The log rank test showed associations of miR-182 with biochemical (p = 0.026) and clinical (p = 0.043) progression-free survival, as also noted on multivariate analysis. A significant independent improvement in the definition of risk of progression was achieved by combining miR-182 expression with Gleason score (p < 0.0001). miR-187 detection in urine provided an independent predictive value for positive biopsy. A prediction model including serum prostate specific antigen, urine PCA3 and miR-187 provided 88.6% sensitivity and 50% specificity (AUC 0.711, p = 0.001).Conclusions: Results show that miR-182 and 187 are promising biomarkers for prostate cancer prognosis to identify patients at risk for progression and for diagnosis to improve the predictive capability of existing biomarkers.