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

描述(申请人提供)：我们已经显示了血液和实体肿瘤中的基因改变和microRNA失调，包括肺癌，这是美国癌症死亡的主要原因。最近，我们在一项完整的螺旋CT筛查试验中研究了肺肿瘤、正常肺组织和具有不同预后的患者的血浆样本中microRNA的表达谱，并进行了广泛的随访。这项试验涉及1025名年龄在50岁或以上的人，他们连续20年或更长时间每天至少抽一包烟。对发病前1-2年、CT检测时以及参加筛查试验的无病吸烟者采集的血浆样本的图谱分析，提供了具有强大预测、诊断和预后潜力的microRNA表达特征(Boeri M.等人)。“组织和血浆中的microRNA特征可以预测计算机断层扫描检测到的肺癌的发展和预后”，Proc。纳特。阿卡德。SCI。美国，2011年3月1日，108：3712-3718)。这些签名在第二次随机螺旋CT试验的独立队列中得到了验证。这些结果表明，microRNAs可以作为肺癌发展和侵袭性的分子预测因子，并对肺癌的治疗具有重要的临床意义。我们建议利用纽约大学(H.Pass博士)和米兰意大利国家癌症研究所(U·帕斯托里诺博士和G.Sozzi博士)的大量患者，通过使用纳米串技术和microRNAs的深度测序来验证这些签名。此外，我们还建议研究在同一组患者的肿瘤、正常组织和血浆中较大的非编码RNA的失调，因为它可以为肺癌的早期发现和预防提供新的强大的生物标志物。

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.