Asbestos Diseases Research Institute (ADRI), Bernie Banton Centre, University of Sydney, New South Wales, Australia.
J Thorac Oncol. 2012 Jul;7(7):1184-91. doi: 10.1097/JTO.0b013e3182572e83.
We investigated the ability of cell-free microRNAs (miRNAs) in plasma and serum to serve as a biomarker for malignant mesothelioma (MM).
Using miRNA microarrays, we profiled plasma samples from MM patients and healthy controls. miRNAs with significantly different abundance between cases and controls were validated in a larger series of MM patients and in an independent series of MM patients using quantitative real-time polymerase chain reaction. Levels of candidate miRNAs were also quantified in MM tumor samples.
We compared cell-free miRNA profiles in plasma from MM patients with healthy controls. Reviewing 90 miRNAs previously reported to be associated with MM, we found that the levels of two miRNAs, miR-29c* and miR-92a, were elevated in plasma samples from MM patients. In addition, we identified 15 novel miRNAs present at significantly higher levels in the plasma of MM patients. Further analysis of candidate miRNAs by real time-quantitative polymerase chain reaction confirmed that one of them, miR-625-3p, was present in significantly higher concentration in plasma/serum from MM patients and was able to discriminate between cases and controls, in both the original and the independent series of patients. MiR-625-3p was also found to be up-regulated in tumor specimens from a group of 18 MM patients, who underwent extrapleural pneumonectomy.
Our data confirm the potential of miR-29c* and miR-92a as candidate tumor markers and reveal that miR-625-3p is a promising novel diagnostic marker for MM.
我们研究了血浆和血清中的无细胞 microRNAs(miRNAs)作为恶性间皮瘤(MM)生物标志物的能力。
使用 miRNA 微阵列,我们对 MM 患者和健康对照者的血浆样本进行了分析。在更大系列的 MM 患者和独立系列的 MM 患者中,使用定量实时聚合酶链反应验证了病例与对照组之间丰度差异显著的 miRNA。还在 MM 肿瘤样本中定量了候选 miRNA 的水平。
我们比较了 MM 患者和健康对照者的血浆无细胞 miRNA 图谱。在回顾了 90 种先前报道与 MM 相关的 miRNA 后,我们发现两种 miRNA(miR-29c* 和 miR-92a)的水平在 MM 患者的血浆样本中升高。此外,我们还发现了 15 种在 MM 患者血浆中水平显著升高的新型 miRNA。通过实时定量聚合酶链反应对候选 miRNA 的进一步分析证实,其中一种 miRNA(miR-625-3p)在 MM 患者的血浆/血清中浓度明显更高,并且能够区分病例和对照者,无论是在原始系列还是独立系列的患者中。在一组 18 名接受胸膜外全肺切除术的 MM 患者的肿瘤标本中也发现了 miR-625-3p 的上调。
我们的数据证实了 miR-29c* 和 miR-92a 作为候选肿瘤标志物的潜力,并表明 miR-625-3p 是 MM 的一种有前途的新型诊断标志物。