Identifying non-coding RNAs for early detection and prevention of lung cancer

描述（由申请人提供）：我们已经显示了造血和实体肿瘤（包括肺癌，美国癌症死亡的主要原因）中的遗传改变和microRNA失调。最近，我们探讨了microRNA表达谱在肺肿瘤，正常肺组织和血浆样本的情况下，涉及到一个完整的螺旋CT筛查试验，广泛的后续活动的可变预后。该试验涉及1025名年龄在50岁或以上的人，他们每天至少吸烟一包香烟，持续20年或更长时间。在疾病发作前1-2年、CT检测时以及在参加筛选试验的无疾病吸烟者中收集的血浆样品的分析提供了具有强预测、诊断和预后潜力的microRNA表达特征（Boeri M.等人“microRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer”，Proc.Nat.Acad. Sci. USA，108：3712-3718，2011年3月1日）。这些特征在第二次随机螺旋CT试验的独立队列中得到验证。这些结果表明microRNA作为肺癌发展和侵袭性的分子预测因子的作用，并对肺癌管理具有重要的临床意义。 我们建议利用纽约大学的大量患者，通过使用NanoString技术和microRNA的深度测序来验证这些特征。通过）和米兰意大利国家癌症研究所（U。Pastorino和G. Sozzi）。此外，我们建议研究同一队列患者的肿瘤，正常组织和血浆中较大非编码RNA的失调，因为它可以为肺癌的早期检测和预防提供新的强大生物标志物。

DESCRIPTION (provided by applicant): We have shown genetic alterations and microRNA dysregulation in hematopoietic and solid tumors, including lung cancer, the major cause of cancer death in the USA. Recently, we explored microRNA expression profiles in lung tumors, normal lung tissues and plasma samples from cases with variable prognosis involved in a completed spiral CT screening trial with extensive follow up. The trial involved 1025 individuals age 50 years or older, who smoked at least a pack of cigarettes a day for 20 years or more. Profiling of plasma samples collected 1-2 years before the onset of disease, at the time of CT detection, and in disease-free smokers enrolled in the screening trial, provided microRNA expression signatures with strong predictive, diagnostic and prognostic potential (Boeri M. et al. "microRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer", Proc. Nat. Acad. Sci. USA, 108:3712-3718, March 1, 2011). These signatures were validated in an independent cohort from a second randomized spiral - CT trial. These results indicate a role of microRNAs as molecular predictors of lung cancer development and aggressiveness and have important clinical implications for lung cancer management. We propose to validate these signatures by using NanoString technology and deep sequencing of microRNAs by taking advantage of large cohorts of patients at NYU (Dr. H. Pass) and at the National Cancer Institute of Italy, Milan, (Drs. U. Pastorino and G. Sozzi). In addition, we propose to investigate the dysregulation of larger non-coding RNAs in the tumors, normal tissues and plasma in the same cohorts of patients, since it could provide novel powerful biomarkers for the early detection and prevention of lung cancer.