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.

项目摘要 肺癌患者的5年生存率仍然很低，约为15%。已经 据估计，肺癌的早期诊断可以提供60-80%的生存益处。国家之肺 筛选试验（NLST）表明，使用每年一次的肺癌死亡率相对降低20%， 低剂量计算机断层扫描（LDCT）筛查与每年胸部X线检查相比。肺的区别 发现的癌症是由于发现了更多的早期肺癌，因为在 组间IIB-IV期癌症的数量。作者得出结论，LDCT筛查减少了肺 癌症死亡率在适当选择的高风险患者。不幸的是，近40%的NLST患者 有一个积极的屏幕在一个点上，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，呼吁增加使用基于血液的生物标志物，以增加 LDCT筛查的诊断准确性，因此迫切需要开发新的非侵入性方法， 例如鉴定血液分子生物标志物，用于肺癌的早期检测。 我们这项提议的直接目标是确定循环非编码RNA（ncRNA）标记物， 使用前瞻性采集的人类血液样本进行肺癌早期检测。很少有研究 比较良性病变和肺癌之间循环miRNA的表达谱。因此 对于验证现有的miRNA研究和鉴定潜在的新的循环miRNA标记物， 肺癌的诊断此外，最近的研究表明，其他类型的小ncRNA，如 小核仁RNA（snoRNA）和转移RNA（tRNA）在癌症发展中起重要作用， 进展然而，没有使用其他类型的循环小ncRNA作为标记物的报道， 肺癌早期诊断 我们假设循环ncRNA可用作肺癌早期检测的生物标志物。 基于下一代小RNA测序，我们已经鉴定了循环血浆中的ncRNA， 在非恶性肿瘤和肺癌生物样本之间的表达有显著差异。此外，委员会认为， 尽管一系列出版物已经报道了用于早期检测的潜在循环miRNA标记物， 肺癌，他们是相当不一致的。为了提高我们的测序能力，评估我们以前的 发现和其他已发表的用于早期检测肺癌的生物标志物。使用前瞻性采集的血浆 样本，在拟议的研究，我们希望达到以下目标：1。衡量的类型和水平 来自非恶性肿瘤和肺癌生物标本的人血浆中的ncRNA表达。2.评价ncRNA - 基于真实的，在非恶性样品和肺癌样品之间可再现地变化的标记物， 时间PCR平台。3.使用独立样本验证和测试ncRNA标记物的预测值。