Profiling genome-wide circulating ncRNAs for the early detection of lung cancer

分析全基因组循环 ncRNA 以早期检测肺癌

• 批准号: 10000889
• 负责人: Youping Deng
• 金额: $ 51.07万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10000889
• 关键词: Adenocarcinoma; Advisory Committees; Age; Anxiety; Benign; Biological Markers; Blood; Blood specimen; Cancer Detection; Chest; Clinic; Clinical; Complement; Data; Development; Diagnosis; Diagnostic tests; Disease; Early Diagnosis; Expression Profiling; Gender; Genetic Transcription; Granuloma; Hamartoma; Hawaii; Health; Human; Human body; Individual; Inflammatory; International; Lesion; Lung; Lung Neoplasms; Lung nodule; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Methods; MicroRNAs; Monitor; Neoadjuvant Therapy; Non-Malignant; Non-Neoplastic Lung Disorder; Patients; Phenotype; Plasma; Play; Positioning Attribute; Predictive Value of Tests; Public Health; Publications; Publishing; Quantitative Reverse Transcriptase PCR; RNA marker; Race; Reporting; Reverse Transcription; Role; Sample Size; Sampling; Series; Serum; Small Nucleolar RNA; Small RNA; Smoking Status; Squamous cell carcinoma; Technology; Testing; Thoracic Radiography; Time; Transfer RNA; Untranslated RNA; Work; X-Ray Computed Tomography; base; blood-based biomarker; circulating microRNA; classification algorithm; cohort; companion diagnostics; computed tomography screening; cost; cost effective; diagnostic accuracy; differential expression; disease diagnosis; early detection biomarkers; genome-wide; high risk; improved; low dose computed tomography; lung cancer screening; molecular marker; mortality; next generation; novel; novel marker; patient response; prospective; screening; screening program; tool; transcriptome sequencing; whole genome

PROJECT SUMMARY The 5-year survival for patients with lung cancer remains dismal at approximately 15%. It has been estimated that early diagnosis of lung cancer can provide a 60-80% survival benefit. The National Lung Screening Trial (NLST) demonstrated a 20% relative reduction in lung cancer mortality with the use of annual low-dose computed tomography (LDCT) screening compared to annual chest x-ray. The difference in lung cancers identified was due to the identification of more early-stage lung cancers, as there was no difference in the number of stage IIB-IV cancers between groups. The authors concluded that LDCT screening reduced lung cancer mortality in appropriately selected high-risk patients. Unfortunately, nearly 40% of patients in the NLST had a positive screen at one point, with 96.4% of these being false positives. Accordingly, the International Association for the Study of Lung Cancer (IASLC) and the Strategic CT Screening Advisory Committee (SSAC) published a position statement calling for the increased use of blood-based biomarkers to augment the diagnostic accuracy of LDCT screening, so it is urgently necessary to develop new non-invasive methods, such as identifying blood molecular biomarkers, for early detection of lung cancer. Our immediate objective for this proposal is to identify circulating non-coding RNA (ncRNA) markers for the early detection of lung cancer using prospectively collected human blood samples. Very few studies have compared the expression profiles of circulating miRNA between benign lesions and lung cancer. Therefore, it is important to validate existing miRNA studies and identify potential novel circulating miRNA markers for early detection of lung cancer. In addition, recent studies have shown that other types of small ncRNAs such as small nucleolar RNAs (snoRNAs) and transfer RNAs (tRNAs) play important roles in cancer development and progression. However, there are no reports which use other types of circulating small ncRNAs as markers for lung cancer early detection. We hypothesize that circulating ncRNA could be used as biomarkers for early detection of lung cancer. Based on next generation small RNA sequencing, we have identified circulating plasma ncRNAs that are significantly differentiated in expression between non-malignant and lung cancer biospecimens. Moreover, although a series of publications have reported the potential circulating miRNA markers for early detection of lung cancer, they are quite inconsistent. In order to increase our sequencing power, evaluate our previous finding and other published biomarkers for early detection of lung cancer. Using prospectively collected plasma samples, in the proposed study, we would like to reach the following aims: 1. Measure the types and levels of ncRNA expression in human plasma from non-malignant and lung cancer biospecimens. 2. Evaluate ncRNA markers that vary reproducibly between non-malignant samples and lung cancer samples based on the real- time PCR platform. 3. Validate and test the predictive value of the ncRNA markers using independent samples.

项目总结 肺癌患者的5年生存率仍然令人沮丧，约为15%。一直以来 据估计，肺癌的早期诊断可以提供60%-80%的生存益处。《国肺》 筛查试验(NLST)显示，使用年度药物可使肺癌死亡率相对降低20% 低剂量计算机断层扫描(LDCT)筛查与年度胸部X光检查的比较。肺的不同 癌症的确定是由于发现了更多的早期肺癌，因为在 两组间IIB-IV期癌症的数量。作者得出结论，LDCT筛查减少了肺部 适当选择高危患者的癌症死亡率。不幸的是，近40%的NLST患者 有一次筛查呈阳性，其中96.4%是假阳性。因此，国际 肺癌研究协会(IASLC)和战略CT筛查咨询委员会 (SSAC)发表了一份立场声明，呼吁增加血液生物标记物的使用，以增强 LDCT筛查的诊断准确性，因此迫切需要开发新的无创方法， 例如识别血液分子生物标记物，用于肺癌的早期检测。 我们这项提议的直接目标是识别循环中的非编码RNA(NcRNA)标记 使用前瞻性采集的人类血液样本早期发现肺癌。很少有研究发现 比较良性病变和肺癌患者外周血中miRNA的表达谱。因此，它 对于验证现有的miRNA研究并确定潜在的早期循环的新的miRNA标记是重要的 肺癌的检测。此外，最近的研究表明，其他类型的小ncRNA，如 小核仁RNAs(SnoRNAs)和转移RNAs(TRNAs)在肿瘤的发生和发展中发挥重要作用 进步。然而，目前还没有使用其他类型的循环小ncRNA作为标记物的报道。 肺癌早期发现。 我们假设循环中的ncRNA可以作为肺癌早期检测的生物标志物。 基于下一代小RNA测序，我们已经识别出循环中的血浆ncRNA是 在非恶性肿瘤和肺癌生物标本中的表达有显著差异。此外， 虽然一系列的出版物报道了潜在的循环中的miRNA标记用于早期检测 肺癌，它们是相当不一致的。为了增加我们的排序能力，评估我们以前的 发现和其他已发表的用于肺癌早期检测的生物标记物。使用预期收集的血浆 样本，在拟议的研究中，我们希望达到以下目标：1.测量 非恶性肿瘤和肺癌患者血浆中ncRNA的表达。2.评估ncRNA 在非恶性样本和肺癌样本之间重复性不同的标记物，基于真实的 时间聚合酶链式反应平台。3.使用独立样本验证和检验ncRNA标记的预测价值。