权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of a multi-analyte diagnostic assay to improve the risk stratification of indeterminate thyroid nodules

开发多分析物诊断测定法以改善不确定甲状腺结节的风险分层

基本信息

批准号：
10684875
负责人：
GISELLE M KNUDSEN
金额：
$ 69.6万
依托单位：
ALAUNUS BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10684875
关键词：
Address Affect Antibodies Autopsy Benchmarking Benign Biological Biological Assay Biological Markers Biological Sciences Biopsy Biopsy Specimen Categories Cells Classification Clinic Clinical Clinical Management Collaborations Contracts Cooperative Human Tissue Network Cytology DNA Sequence Alteration Data Detection Development Diagnosis Diagnostic Diagnostic Imaging Diagnostic tests Disease Documentation Early Diagnosis Excision Feasibility Studies Fine needle aspiration biopsy Fluorogenic Substrate Frequencies Genetic Risk Genomics Goals Guidelines Image Indiana Industry Standard Institutional Review Boards Laboratories Lesion Malignant - descriptor Malignant Neoplasms Malignant neoplasm of thyroid Measures Molecular Molecular Analysis Monitor Nodule Nucleotides Operative Surgical Procedures Pathologic Pathology Patient risk Patients Peptide Hydrolases Performance Persons Phase Predictive Value Prevalence Prospective cohort Proteins Proteolysis Proteomics Readiness Reporting Resected Retrospective cohort Risk Risk Marker Sampling Science Scientific Advances and Accomplishments Sensitivity and Specificity Source Specificity Technology Testing Thyroid Gland Thyroid Nodule Thyroidectomy Tissue Sample Tissues Ultrasonography United States Universities Unnecessary Surgery Validation Work biobank biomarker discovery cancer invasiveness clinical center clinical decision-making clinical practice cohort commercialization cost detection limit diagnostic accuracy diagnostic assay diagnostic biomarker diagnostic tool enzyme activity improved innovation mortality novel marker patient stratification precision medicine premalignant prognostic programs prospective rapid test risk stratification standard of care technology validation tool ultrasound validation studies

项目摘要

Abstract Widespread use of sensitive imaging in clinical practice has resulted in incidental thyroid nodules being discovered with increasing frequency, creating a unique opportunity to detect and remove lesions at early stages of malignancy. The majority of these incidental nodules remain benign and asymptomatic, but 10-20% are found to be malignant on surgical excision, resulting in a critical need for improved diagnostics, as 75% of patients currently undergo unnecessary thyroidectomies to remove benign nodules. The current standard of care includes collecting a tissue biopsy by ultrasound-guided fine needle aspiration: these samples are tested by cytology, which looks for aberrant cells, and for genetic risk markers. These diagnostic tests are characterized by poor specificity, and a third of all tested nodules are still classified as indeterminate and need to be resected for a pathological diagnosis. We originally hypothesized that dysregulated proteolysis, a type of enzyme activity that is a hallmark of invasive cancer, might yield discriminating levels of activity in FNA tissue from benign and malignant nodules. In Phase I work, we leveraged the Alaunus Biosciences, Inc. diagnostic pipeline, a platform that allows innovative proteomics-based biomarker discovery, to identify and characterize a set of protease activities (functional markers) that are significantly increased in malignant nodules. We then developed fluorogenic substrate assays to monitor these activities using small volumes of biological samples. In parallel, we also discovered additional mass-based markers that can be measured with standard antibody-based assays. Our investigational multi-analyte diagnostic assay has the potential to differentiate malignant from benign thyroid tissue with sensitivity and specificity >90%. In this Phase II proposal, we aim to perform technical and clinical validation studies required to advance the assay to readiness for clinical use in the early diagnosis of indeterminate thyroid nodules. In Aim 1, we will benchmark the clinical utility of our selected protein and functional biomarkers in surgical tissue to evaluate scoring, establish diagnostic thresholds, and report on key assay parameters. In Aim 2, we will perform a comprehensive technical assessment of the laboratory performance of the assay to satisfy industry standards. In Aim 3, we will create an independent cohort of FNA tissue samples, through our IRB- approved biobanking efforts at UCSF, UCLA and IU, to be used for a robust prospective validation of the clinical usefulness of the assay. Our goal is to develop a rapid assay that improves patient stratification over current standard diagnostic markers, guides clinical decision-making to avoid unnecessary surgical intervention, and transforms the clinical management of these challenging lesions.

摘要