Circulating miRNAs are correlated with tumor progression in prostate cancer
Circulating miRNAs are correlated with tumor progression in prostate cancer
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DOI：
10.1002/ijc.25376
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发表时间：
2011-02-01
影响因子：
6.4
通讯作者：
Sueltmann, Holger
中科院分区：
文献类型：
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作者：
Brase, Jan C.;Johannes, Marc;Sueltmann, Holger
循环中的miRNAs是近年来发现的一种实用的、有前途的生物标志物，可用于各种肿瘤的无创性诊断。然而，没有发现无细胞的miRNA与上皮癌的临床病理变量相关。为了更多地了解循环miRNA在前列腺癌中的潜在临床相关性，我们筛选了来自转移性（n = 7）和局限性前列腺癌（n = 14）患者的血清样品中的667种miRNA。各种miRNA在转移性疾病患者的血清中高度丰富，并且选择五种上调的miRNA（miRNA-375、miRNA-9*、miRNA-141、miRNA-200 b和miRNA-516 a-3 p）用于进一步验证。在第一个验证研究（n = 45）中，在从不同前列腺癌风险组中前瞻性收集的血清集中分析选定的miRNA。当分析不同的临床病理变量时，大多数选择的miRNAs与不良风险因素显著相关。循环中的miRNA-375和miRNA-141被证明是高危肿瘤最明显的标志物。在第二项独立验证研究（n = 71）中，它们的水平也与高Gleason评分或淋巴结阳性状态相关。此外，在72个前列腺组织样本中监测了miRNA-375和miRNA-141的表达水平（36个肿瘤与36个良性）。这两种miRNA在所有样品中均高度表达，并且与正常组织相比，在肿瘤中显著上调。总体而言，我们的观察结果表明，miRNA-375和miRNA-141在前列腺癌标本中的表达增强，并且它们释放到血液中与晚期癌症疾病进一步相关。
Circulating miRNAs have recently been indicated as practicable and promising biomarkers for noninvasive diagnosis in various tumor entities. However, cell-free miRNAs have not been found to correlate with clinicopathological variables in epithelial carcinomas. To learn more about the potential clinical relevance of circulating miRNAs in prostate cancer, we screened 667 miRNAs in serum samples from patients with metastatic (n = 7) and localized prostate cancer (n = 14). Various miRNAs were highly abundant in the sera of patients with metastatic disease, and five upregulated miRNAs (miRNA-375, miRNA-9*, miRNA-141, miRNA-200b and miRNA-516a-3p) were selected for further validation. In the first validation study (n = 45), selected miRNAs were analyzed in a prospectively collected serum set taken from different prostate cancer risk groups. Most of the selected miRNAs were significantly correlated with adverse risk factors when different clinicopathological variables were analyzed. Circulating miRNA-375 and miRNA-141 turned out to be the most pronounced markers for high-risk tumors. Their levels also correlated with high Gleason score or lymph-node positive status in a second independent validation study (n = 71). In addition, the expression levels of miRNA-375 and miRNA-141 were monitored in 72 prostate tissue samples (36 tumor vs. 36 benign). Both miRNAs were highly expressed in all samples and significantly upregulated in the tumors compared to normal tissues. Overall, our observations suggest that miRNA-375 and miRNA-141 expression is enhanced in prostate cancer specimens and their release into the blood is further associated with advanced cancer disease.