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Noninvasive, Uniplex, Molecular, Pathomic Urinary Assay for Detection of Prostate Cancer

用于检测前列腺癌的无创、单一、分子、病理性尿液分析

基本信息

批准号：
10427409
负责人：
MATHEW laxman THAKUR
金额：
$ 58.2万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10427409
关键词：
Advocate Attention Benign Benign Prostatic Hypertrophy Biochemistry Biological Assay Biological Markers Biopsy Blinded Blood Breast Cancer Etiology Cancer Patient Cells Cessation of life Clinical Development Diagnosis Diagnostic Diagnostic tests Digital Rectal Examination Disease FDA approved Fingers Fluorescence Genomics Goals Gold HOXC6 gene Healthcare Histology Human Image Indolent Investigation Label Life Literature Malignant - descriptor Malignant Neoplasms Malignant neoplasm of prostate Measures Messenger RNA Methods Molecular Molecular Profiling Morbidity - disease rate Names North America Pathology Patients Peptides Predictive Value Procedures Prostate Prostate-Specific Antigen Proteins Research Personnel Role Sampling Schedule Screening for Prostate Cancer Sensitivity and Specificity Serology Serum Solid Specificity Surface Testing Translating Transrectal Ultrasound United States National Institutes of Health Urine VIPR1 gene cancer biomarkers cancer cell cancer diagnosis clinical practice design detection assay diagnostic biomarker efficacy evaluation fluorophore in vivo innovation malignant breast neoplasm men minimally invasive novel optical imaging overexpression overtreatment prostate biopsy prostate cancer cell receptor serum PSA stem tumor molecular fingerprint ultrasound urinary

项目摘要

Abstract: Despite the advances in understanding its genomic and molecular basis, prostate cancer (PCa) remains the most commonly diagnosed solid malignancy in men in the US and the second leading cause of cancer death. Currently, the only established method to diagnose PCa is an invasive transrectal ultrasound prostate biopsy. The majority (>66%) of biopsies show benign pathology at the expense of patient morbidity and healthcare dollars. There remains, therefore, an unmet need for a simple and non-invasive approach that will definitively diagnose PCa, determine if it is aggressive, indolent or benign and help guide its management. The era of molecular profiling has drawn much attention to genomic analysis of malignant PCa cells shed in blood and urine. In two such assays, the PCA3 and SelectMDx approved by FDA, urine is collected after DRE, malignant cells isolated and characterized by multiplex genomic finger prints of PCa. Although innovative, PCA3 test is not widely used, primarily due to its wide range (62%-94%) of sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV). Furthermore, the clinical utility of SelectMDx and a frequently advocated serum 4Kscore test, remains uncertain. There is robust literature demonstrating that VPAC receptors are expressed on PCa cells. With NIH/NCI support, we designed and labeled a VPAC specific peptide with Cu-64 that allowed us to image PCa successfully in humans. We then hypothesized that PCa cells, shed in voided urine of PCa patients, without prostate stimulation by DRE, can be imaged optically by targeting VPAC receptors, using the same peptide labeled with a fluorophore. Our preliminary results of >250 de-identified urine samples, collected from patients with PCa, BPH and normal cases, are encouraging (sensitivity >98%) and are consistent with our hypothesis. In this investigation we propose to obtain critical information that will be required for the development of this promising noninvasive urine assay as a PCa diagnostic test. Our specific aims are 1) To determine sensitivity, specificity, positive predictive (PPV), and negative predictive value (NPV) of the molecular urinary assay for men with known PCa and negative controls; 2) To examine the efficacy of the assay in the management of patients with previous negative biopsy for PCa but have persistently elevated PSA and are scheduled for TRUS biopsy; 3) To establish if a) the malignant cells as a percent of total cells shed in the urine, b) the fluorescence intensity around malignant cells, and c) the VPAC protein quantity in shed malignant cells correlate with the aggressiveness of the disease; 4) To assess the role of this molecular urine assay in the management patients on active surveillance; and 5) To determine if a preservative is required for urine storage. This simple, reliable and patient-friendly uniplex assay will a) detect active, aggressive or indolent PCa, b) save patients from over diagnosis and over treatment, c) reduce the number of unnecessary biopsies and associated patient morbidity, and d) save millions of healthcare dollars.

摘要：尽管对前列腺癌（PCa）的基因组和分子基础的了解有所进展，但前列腺癌（PCa）