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: 10477044
• 负责人: Youping Deng
• 金额: $ 48.17万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10477044
• 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; diagnostic tool; diagnostic value; 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; treatment response; whole genome; 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; diagnostic tool; diagnostic value; 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; treatment response; 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年生存率仍然令人沮丧，约15％。它一直 估计肺癌的早期诊断可以提供60-80％的生存益处。国家肺 筛查试验（NLST）表明，使用年度肺癌死亡率相对降低20％ 与年度胸部X射线相比，低剂量计算机断层扫描（LDCT）筛选。肺的差异 确定的癌症是由于对更多早期肺癌的鉴定，因为没有差异 组之间的IIB-IV阶段癌的数量。作者得出的结论是，LDCT筛查减少了肺 适当选择的高危患者中的癌症死亡率。不幸的是，近40％的NL患者 在某一时刻有一个正面的屏幕，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）发表了一份职位声明，要求增加使用基于血液的生物标志物来增加 LDCT筛选的诊断准确性，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，以早期检测到肺癌。 我们对该提案的直接目标是确定循环的非编码RNA（NCRNA）标记 使用前瞻性收集的人类血液样本对肺癌的早期检测。很少有研究 比较了良性病变和肺癌之间循环miRNA的表达谱。因此，它 验证现有的miRNA研究并确定早期的潜在新型miRNA标记很重要 检测肺癌。此外，最近的研究表明，其他类型的小NCRNA，例如 小核仁RNA（SNORNA）和转移RNA（TRNA）在癌症发展和 进展。但是，没有报告使用其他类型的循环小NCRNA作为标记 肺癌早期检测。 我们假设循环NCRNA可以用作早期检测肺癌的生物标志物。 基于下一代小的RNA测序，我们已经确定了循环等离子体NCRNA 非恶性和肺癌生物测量之间的表达显着分化。而且， 尽管一系列出版物报道了潜在的循环miRNA标记，以提早发现 肺癌，它们是非常不一致的。为了提高我们的测序能力，请评估我们以前的 发现和其他已发表的生物标志物，用于早期发现肺癌。使用前瞻性收集的等离子体 样本，在拟议的研究中，我们想达到以下目的：1。测量的类型和水平 来自非恶性和肺癌生物测量的人血浆中的NCRNA表达。 2。评估NCRNA 基于实现 时间PCR平台。 3。使用独立样品验证和测试NCRNA标记的预测值。