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

• 批准号: 8306737
• 负责人: Anil Vachani
• 金额: $ 18.1万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306737
• 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

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).

描述（由申请人提供）：非小细胞肺癌（NSCLC）是西方国家恶性疾病导致过早死亡的最常见原因。早期发现后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射线或计算机轴向断层扫描（CT）确定病因不明的肺结节患者的诊断是一个非常常见和重要的临床问题。可以更准确地确定患有肺结节的患者中恶性疾病风险的血液测试将是极其有价值的，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扫描而具有非常重要的经济意义。我们以前假设，诊断基因表达谱可以在肺癌患者的外周血中确定。为了支持这一假设，我们最近发表了一项研究，表明与高危吸烟者和戒烟者的适当对照组相比，可以确定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名对照者中收获的外周血单核细胞（PBMC），我们鉴定了29个基因签名，其提供了86%的总体辨别准确度。NSCLC组中受影响的特异性免疫功能途径包括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，该系统提供了更高的mRNA稳定性和更容易用于常规临床使用的平台。我们的工作将集中在用Paxgene系统从外周血中开发外周血基因表达特征（Aim 1）和评估外周血基因表达与多种新型血清生物标志物的组合（Aim 2）。如果成功的话，这些检测可以整合到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CT扫描。如果有足够的敏感性和特异性，这种测试可能会扩展到其他高风险人群（石棉暴露的吸烟者，重度吸烟者等）的筛查。