MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer
MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer
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DOI：
10.1073/pnas.1100048108
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发表时间：
2011-03-01
影响因子：
11.1
通讯作者：
Sozzi, Gabriella
中科院分区：
文献类型：
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作者：
Boeri, Mattia;Verri, Carla;Sozzi, Gabriella
目前，许多随机试验正在测试计算机断层扫描（CT）筛查对重度吸烟者早期肺癌检测的有效性。关键问题仍然是不必要的治疗频率和对死亡率的影响，这表明需要侵袭性疾病的生物标志物。我们探索了肺肿瘤、正常肺组织和血浆样本的 microRNA (miRNA) 表达谱，这些样本来自于一项完整的螺旋 CT 筛查试验和广泛的随访中确定的预后可变的病例。 miRNA 表达模式显着区分：（i）来自正常肺组织的肿瘤，（ii）肿瘤组织学和生长速度，（iii）临床结果，以及（iv）肺癌 CT 检测年份。有趣的是，正常肺组织中的 miRNA 谱也显示出与临床特征的显着关联，表明宽松的微环境对肿瘤发展的影响。对发病前 1-2 年、CT 检测时收集的血浆样本以及参加筛选试验的无病吸烟者进行的 miRNA 表达分析，产生了具有强大预测、诊断和预后潜力的 miRNA 特征（ROC 曲线下面积 >= 0.85）。这些特征在第二次随机螺旋 CT 试验的独立队列中得到了验证。这些结果表明肺组织和血浆中的 miRNA 作为肺癌发展和侵袭性的分子预测因子的作用，并对肺癌治疗具有理论和临床意义。
The efficacy of computed tomography (CT) screening for early lung cancer detection in heavy smokers is currently being tested by a number of randomized trials. Critical issues remain the frequency of unnecessary treatments and impact on mortality, indicating the need for biomarkers of aggressive disease. We explored microRNA (miRNA) expression profiles of lung tumors, normal lung tissues and plasma samples from cases with variable prognosis identified in a completed spiral-CT screening trial with extensive follow-up. miRNA expression patterns significantly distinguished: (i) tumors from normal lung tissues, (ii) tumor histology and growth rate, (iii) clinical outcome, and (iv) year of lung cancer CT detection. Interestingly, miRNA profiles in normal lung tissues also displayed remarkable associations with clinical features, suggesting the influence of a permissive microenvironment for tumor development. miRNA expression analyses in plasma samples collected 1-2 y before the onset of disease, at the time of CT detection and in disease-free smokers enrolled in the screening trial, resulted in the generation of miRNA signatures with strong predictive, diagnostic, and prognostic potential (area under the ROC curve >= 0.85). These signatures were validated in an independent cohort from a second randomized spiral-CT trial. These results indicate a role for miRNAs in lung tissues and plasma as molecular predictors of lung cancer development and aggressiveness and have theoretical and clinical implication for lung cancer management.