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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

基本信息

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
项目类别：
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

项目摘要

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