Developing a CLIA compliant LDT for detecting plasma piR-Ls/pfeRNAs to distinguish benign and malignant lung nodules

开发符合 CLIA 标准的 LDT，用于检测血浆 piR-Ls/pfeRNA，以区分良性和恶性肺结节

• 批准号: 9908056
• 负责人: MALCOLM V BROCK
• 金额: $ 33.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-05 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908056
• 关键词: Area; Benign; Biological; Biological Assay; Biological Markers; Biopsy; CLIA certified; Cancer Etiology; Cessation of life; Clinical; Clinical Markers; Clinical Research; Country; Data; Databases; Decision Making; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Early Diagnosis; Enrollment; Ensure; Equipment; Excision; Future; High Prevalence; Histologic; Hospitals; In Vitro; Laboratories; Lung CAT Scan; Lung nodule; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Medical; Methods; Non-Small-Cell Lung Carcinoma; Nucleic Acids; Patients; Performance; Physicians; Plasma; Play; Reagent; Reporting; Research Personnel; Role; Sampling; Scientist; Sensitivity and Specificity; Smoker; Specimen; Structure of parenchyma of lung; Surgeon; Survival Rate; Technology; Testing; Time; Tissues; Validation; X-Ray Computed Tomography; base; cohort; deep sequencing; diagnostic assay; early detection biomarkers; early phase clinical trial; improved; in vivo; laboratory equipment; lung cancer screening; molecular diagnostics; mortality; multidisciplinary; new technology; next generation; outcome forecast; piRNA; protein function; response; screening program; tumorigenesis

Project Summary: Lung cancer is the leading cause of cancer-related death in the U.S., in large part, because the diagnosis tends to be made after the cancer has progressed to its most advanced stages. However, current diagnostic techniques for detecting early-stage non-small cell lung cancer (NSCLC) are either invasive or have poor accuracy. We recently reported that piRNA-like sncRNAs (piR-Ls) and protein function effector sncRNAs (pfeRNAs) play critical roles in the tumorigenesis and differentiation of lung cancer. We have developed a novel technology for accurately and robustly measuring piR-Ls and pfeRNAs in plasma. We also have identified 2 piR-Ls and 6 pfeRNAs as promising non-invasive biomarkers using next generation sncRNAs deep sequencing of 119 biospecimens, including (i) plasma from healthy controls (ii) patient plasma with the matched, corresponding histologically proven NSCLC tissue as well as histologically normal adjacent lung tissue from patients with Stage I/II NSCLC (iii) plasma from patients with both biopsy proven benign and malignant lung nodules. Furthermore, we validated these biomarkers in 352 clinical plasma specimens, including 77 healthy controls, 44 patients with benign disease as well as 231 patients with malignant lung nodules. Moreover, we formulated prediction rules for our assay in detecting early-stage NSCLC. Using only plasma, we were able to: (1) differentiate patients with and without lung nodules, with a sensitivity and specificity of 98.5% and 98.7%, respectively (an important clinical assay needed in remote, impoverished areas of the world with a high prevalence of smokers but no access to CT scanning); (2) differentiate patients who had malignant versus benign lung nodules, with a sensitivity and specificity of 96.5% and 72.7%, respectively (important for economically advanced countries enrolling smokers to CT lung cancer screening programs). These data strongly suggest that our panel of 2 piR-Ls and 6 pfeRNAs are non-invasive putative biomarkers for detecting early-stage lung cancers. Our multi-disciplinary collaborative team consists of a physician-scientist, basic researchers, a physician-scientist in the CLIA-certified laboratory, statisticians, and a commercial developer. This team will develop a CLIA compliant LDT for validating our nucleic- acid-based existing assay which now has been tested as valid in over 460 clinical specimens. The technologies that we will utilize for our testing are currently FDA-cleared for use in clinical laboratories, and the equipment as well as all reagents for our assays already are used in in-vitro-diagnostic testing. Our collaborative team aims to develop a molecular diagnostic assay that can be integrated into future clinical trials for the early detection of NSCLC, and ultimately, improve the dismal survival rates of that disease.

项目总结: