Peripheral Blood Gene Expression for the Diagnosis of Indeterminate Lung Nodules

外周血基因表达用于诊断不确定性肺结节

基本信息

批准号：
8191990
负责人：
Anil Vachani
金额：
$ 23.31万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8191990
关键词：
Adopted Affect Algorithms Apoptosis Area Asbestos Autoantibodies Benign Biological Assay Biological Markers Biopsy Blood Blood Tests Cancer Detection Cancer Patient Cell Size Cessation of life Chest Clinical Collection Communities Control Groups Country Data Development Diagnosis Diagnostic Discrimination Disease Early Diagnosis Etiology Ficoll Gene Expression Gene Expression Profile Genes Goals Harvest Human Resources Image Internist Lung nodule Malignant - descriptor Malignant neoplasm of lung Messenger RNA Modality Molecular Profiling Nodule Non-Small-Cell Lung Carcinoma Operative Surgical Procedures Pathway interactions Patients Peripheral Blood Mononuclear Cell Phagocytosis Population Positron-Emission Tomography Process Proteins Publishing Receptor Signaling Research Research Activity Risk Sampling Scanning Screening procedure Serum Serum Markers Site Smoker Smoking Status Standardization Surgeon System T-Cell Receptor Technology Testing Thoracic Radiography Time Unnecessary Surgery Validation Work X-Ray Computed Tomography anticancer research base cell type cytokine diagnostic accuracy economic implication effective therapy high risk immune function improved mRNA Stability macrophage monocyte neoplastic cell novel peripheral blood premature prevent sample collection tumor

项目摘要

DESCRIPTION (provided by applicant): Non-small cell lung cancer (NSCLC) is the most common cause of premature death from malignant disease in western countries. Early detection followed by surgery remains the most effective treatment. The diagnosis of patients who have lung nodules of unknown etiology identified on screening chest X-rays or computerized axial tomography (CT) scans, is a very common and important clinical problem for internists, surgeons, and pulmonologists. A blood test that could more accurately determine the risk of malignant disease in patients with lung nodules would be extremely valuable and have very important economic implications by reducing unnecessary surgery, biopsies, Positron Emission Tomography (PET) scans, and/or repeated CT scans. We previously hypothesized that a diagnostic gene expression profile can be identified in the peripheral blood of lung cancer patients. In support of this hypothesis, we recently published a study showing that differences in blood gene expression profiles can be identified that accurately identify patients with NSCLC when compared to the appropriate control group of high-risk smokers and ex-smokers. Using peripheral blood mononuclear cells (PBMC) harvested from 137 NSCLC subjects and 91 controls, we identified a 29-gene signature that provides an overall discrimination accuracy of 86%. Specific immune function pathways that were affected in the NSCLC group included alterations in T-cell receptor signaling and apoptosis, and macrophage and monocyte phagocytosis. The goal of this proposal is to expand these preliminary studies to the Paxgene blood collection system, which provides greater mRNA stability and a platform more easily adopted for routine clinical use. We will focus our work on developing a peripheral blood gene expression signature from peripheral blood with the Paxgene system (Aim 1) and on evaluating the combination of peripheral blood gene expression with multiple novel serum biomarkers (Aim 2). If successful, these assays could be integrated into a diagnostic algorithm for patients with indeterminate lung nodules and used to prevent needless surgery and repetitive CT scans. If sufficiently sensitive and specific, it is possible that this test could be extended to screening of other high-risk populations (smokers with asbestos exposure, heavy smokers, etc). PUBLIC HEALTH RELEVANCE: Lung nodules of unknown etiology are discovered frequently on chest x-rays or CT scans but only a small fraction of these lung nodules are found to be lung cancers. Currently, the only way to differentiate benign from malignant nodules is an invasive biopsy, surgery, or prolonged observation with repeated scanning. Given these facts, the development of a blood test that could more accurately determine the risk of malignant disease in patients with lung nodules would be extremely valuable and have very important economic implications by reducing unnecessary surgery, biopsies, Positron Emission Tomography (PET) imaging, and/or repeated CT scans.

描述（由申请人提供）：非小细胞肺癌（NSCLC）是西方国家恶性疾病过早死亡的最常见原因。早期发现并进行手术仍然是最有效的治疗方法。对于内科医生、外科医生和肺科医生来说，通过筛查胸部 X 光或计算机轴向断层扫描 (CT) 扫描发现患有不明原因肺结节的患者的诊断是一个非常常见且重要的临床问题。能够更准确地确定肺结节患者恶性疾病风险的血液测试将非常有价值，并且通过减少不必要的手术、活检、正电子发射断层扫描 (PET) 扫描和/或重复 CT 扫描，具有非常重要的经济意义。我们之前假设可以在肺癌患者的外周血中鉴定诊断基因表达谱。为了支持这一假设，我们最近发表的一项研究表明，与高危吸烟者和戒烟者的适当对照组相比，可以识别血液基因表达谱的差异，从而准确识别 NSCLC 患者。使用从 137 名 NSCLC 受试者和 91 名对照者中采集的外周血单核细胞 (PBMC)，我们确定了 29 个基因特征，总体区分准确度为 86%。 NSCLC 组中受影响的特定免疫功能途径包括 T 细胞受体信号传导和细胞凋亡以及巨噬细胞和单核细胞吞噬作用的改变。该提案的目标是将这些初步研究扩展到 Paxgene 血液采集系统，该系统提供更高的 mRNA 稳定性和更容易用于常规临床使用的平台。我们的工作重点是使用 Paxgene 系统开发外周血基因表达特征（目标 1），并评估外周血基因表达与多种新型血清生物标志物的组合（目标 2）。如果成功，这些测定可以整合到针对不确定肺结节患者的诊断算法中，并用于防止不必要的手术和重复的 CT 扫描。如果足够灵敏和特异性，该测试有可能扩展到其他高风险人群（接触石棉的吸烟者、重度吸烟者等）的筛查。公共卫生相关性：胸部 X 光检查或 CT 扫描经常发现病因不明的肺结节，但这些肺结节中只有一小部分被发现是肺癌。目前，区分良恶性结节的唯一方法是侵入性活检、手术或反复扫描的长期观察。鉴于这些事实，开发一种能够更准确地确定肺结节患者恶性疾病风险的血液测试将非常有价值，并且通过减少不必要的手术、活组织检查、正电子发射断层扫描（PET）成像、和/或重复 CT 扫描。