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

鉴定非编码 RNA 以早期检测和预防肺癌

基本信息

批准号：
8504396
负责人：
CARLO M CROCE
金额：
$ 96.71万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-02 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8504396
关键词：
Advanced Malignant Neoplasm Adverse effects Affect Age B-Lymphocytes Behavior Biological Biological Markers Biology Blood Breast Burkitt Lymphoma Cancer Etiology Cancer Patient Cells Cessation of life Chest Chronic Chronic Lymphocytic Leukemia Cigarette Clinical Colorectal Cancer Conflict (Psychology)DNA Sequence Rearrangement Data Defect Detection Development Diagnostic Disease Early Diagnosis Enrollment Epigenetic Process Etiology FHIT gene Family Frequencies Functional RNA Gene Expression Gene Proteins Genes Genetic Goals Hematopoietic Neoplasms Human Individual Indolent Italy Lead Lesion Link Lung Lung Adenocarcinoma Lung Neoplasms Lymphocyte Lymphoma Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung MicroRNAs Molecular Molecular Profiling Mutation National Cancer Institute Natural History Normal tissue morphology Observational Study Oncogenic Onset of illness Organism PTEN gene Pathogenesis Pathway interactions Patients Pattern Plasma Play Procedures Publications Publishing RNA Randomized Regulation Reporting Risk Role Sampling Scanning Smoke Smoker Solid Neoplasm Spiral Computed Tomography Sputum Structure of parenchyma of lung Techniques Technology Time Tissues Tobacco Translations Tumor Suppressor Proteins Untranslated RNA Urine X-Ray Computed Tomography aged arm cancer diagnosis cohort cost deep sequencing follow-up high risk insight lung cancer prevention lung cancer screening lung carcinogenesis mRNA Expression man member mortality nano-string neoplastic novel outcome forecast prognostic protein expression public health relevance screening tool tumor

项目摘要

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.

描述（由申请人提供）：我们已经展示了造血系统和实体瘤中的基因改变和 microRNA 失调，包括肺癌，肺癌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 筛查试验中探索了肺肿瘤、正常肺组织和预后可变病例血浆样本中的 microRNA 表达谱，并进行了广泛的随访。该试验涉及 1025 名 50 岁或以上的人，他们每天至少吸一包烟，持续 20 年或更长时间。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收集的血浆样本进行分析，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 特征可预测计算机断层扫描检测到的肺癌的发展和预后”，美国科学院院刊，108：3712-3718。 1, 2011）。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 microRNA 作为肺癌发展和侵袭性的分子预测因子的作用，并对肺癌治疗具有重要的临床意义。我们建议通过使用 NanoString 技术和 microRNA 深度测序来验证这些特征，方法是利用纽约大学（H. Pass 博士）和米兰意大利国家癌症研究所（U. Pastorino 博士和G.索齐）。此外，我们建议研究同一组患者的肿瘤、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的生物标志物。