Dept of Medical Oncology, Puerta de Hierro Majadahonda University Hospital, C/Joaquín Rodrigo, 2; E-28222 Majadahonda, Madrid, Spain.
Eur Respir J. 2011 Mar;37(3):617-23. doi: 10.1183/09031936.00029610. Epub 2010 Jul 1.
The identification of tumour biomarkers that detect the presence of disease using noninvasive diagnostic procedures is a key part of cancer research. We determined in plasma the vesicle-related microRNA (miRNA) expression profile of nonsmall cell lung cancer (NSCLC) and evaluate whether plasma miRNAs can be both discriminating (between patients and healthy controls) and prognostic markers. 365 human miRNAs were analysed by Taqman® low-density arrays (Applied Biosystems, Foster City, CA, USA) in the plasma from 28 NSCLC patients and 20 controls. Five selected miRNAs (let-7f, miR-20b, miR-30e-3p, miR-223 and miR-301) were validated independently by real-time PCR in plasma from 78 NSCLC and 48 controls and correlated with pathologic parameters and survival. Levels of let-7f, miR-20b and miR-30e-3p were decreased in plasma vesicles of NSCLC patients. Moreover, levels of let-7f and miR-30e-3p distinguished between two groups of patients for stage of disease and therefore possibility of surgery. Plasma levels of miR-30e-3p and let-7f were associated with short disease-free survival and overall survival, respectively. NSCLC patients and healthy controls differ in vesicle-related miRNAs in plasma. Levels of let-7f and miR-30e-3p in NSCLC patients are associated with poor outcome. Thus, plasma vesicle-related miRNAs obtained by noninvasive methods could serve as circulating tumour biomarkers of discriminating and prognostic value.
使用非侵入性诊断程序来识别肿瘤标志物以检测疾病的存在是癌症研究的关键部分。我们确定了非小细胞肺癌(NSCLC)患者血浆中与囊泡相关的 microRNA(miRNA)表达谱,并评估了血浆 miRNAs 是否既可以作为区分(患者与健康对照)标志物,又可以作为预后标志物。应用 Taqman®低密度阵列(Applied Biosystems,Foster City,CA,USA)分析了 28 名 NSCLC 患者和 20 名对照者血浆中的 365 种 miRNA。在 78 名 NSCLC 患者和 48 名对照者的血浆中,通过实时 PCR 独立验证了 5 种选定的 miRNA(let-7f、miR-20b、miR-30e-3p、miR-223 和 miR-301),并与病理参数和生存相关。在 NSCLC 患者的血浆囊泡中,let-7f、miR-20b 和 miR-30e-3p 的水平降低。此外,let-7f 和 miR-30e-3p 的水平可区分两组患者的疾病分期,因此可能进行手术。miR-30e-3p 和 let-7f 的血浆水平分别与无病生存和总生存时间短相关。NSCLC 患者和健康对照者的血浆中与囊泡相关的 miRNA 存在差异。NSCLC 患者中 let-7f 和 miR-30e-3p 的水平与不良预后相关。因此,通过非侵入性方法获得的血浆囊泡相关 miRNA 可作为具有区分和预后价值的循环肿瘤生物标志物。