Noninvasive Risk Stratification of Prostate Cancer Using Cell-Free Nucleic Acids

使用无细胞核酸对前列腺癌进行无创风险分层

基本信息

批准号：
10217044
负责人：
Wei Gu
金额：
$ 28.37万
依托单位：
STANFORD 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：
2020-11-16 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10217044
关键词：
Aftercare Alleles Area Bioinformatics Biological Markers Biometry Biopsy CRISPR/Cas technology California Cancer Biology Cancer Detection Cancer Diagnostics Cancer Etiology Cancer Patient Cells Clinical Clinical Management Clinical Research Communities Copy Number Polymorphism Cross-Sectional Studies DNA DNA Markers Data Collection Detection Development Development Plans Diagnosis Diagnostic Doctor of Philosophy Environment Five-Year Plans Fostering Foundations Genes Genomics Goals High-Throughput Nucleotide Sequencing Hypermethylation Incidental Findings Individual K-Series Research Career Programs Knowledge Laboratories Malignant Neoplasms Malignant neoplasm of prostate Measures Medicine Mentors Mentorship Metagenomics Methods Methylation Molecular Noise Non-Malignant Nucleic Acids Oncology Operative Surgical Procedures Pathologist Pathology Patients Pattern Physicians Plasma Point Mutation Positioning Attribute Promoter Regions Prostate Prostatectomy Public Health Publishing Radical Prostatectomy Research Research Design Risk Risk Assessment Sampling San Francisco Scientist Screening for cancer Site Techniques Testing Tissues Training Translating Universities Urine Validation Work active method base cancer biomarkers cancer care career development cell free DNA comorbidity early screening experience genome sequencing genome-wide high risk improved innovation men methylation biomarker methylation pattern molecular pathology mortality multidisciplinary new technology next generation sequencing noninvasive diagnosis novel overtreatment prenatal preservation prognostic promoter prostate cancer progression prostate cancer risk prostate surgery risk stratification side effect skills success tool tumor tumor DNA whole genome

项目摘要

PROJECT SUMMARY/ABSTRACT Every year, more than 161,000 men in the U.S. are diagnosed with prostate cancer. While prostate cancer remains a significant cause of cancer related mortality, early screening efforts are hampered by the fact that the majority of cases are not imminently deadly and active treatments or re-biopsies have adverse side effects. The goal of this proposal is to pioneer new non-invasive diagnostics to distinguish between high-risk versus low-risk prostate cancers in order to guide clinical management. The core hypothesis of this proposal is that copy number variations and methylation markers can be found non-invasively in circulating nucleic acids as a surrogate for invasive tissue markers, and these markers can risk stratify localized prostate cancers. The first aim will evaluate two non-invasive biomarkers for prostate cancer using next-generation sequencing (NGS)-based approaches. Plasma and urine samples will be tested for copy number variations and methylation markers, and compared against concurrent prostate cancer tissue taken from prostate surgery. The second aim will evaluate the non-invasive approaches in the first aim for the ability to risk stratify localized prostate cancer in a cross-sectional study. In this K08 Mentored Clinical Scientist Research Career Development Award application, the applicant, Wei Gu, MD, PhD, is a board certified Clinical Pathologist at UCSF Department of Laboratory Medicine. This proposal encompasses a five-year plan to enhance his research and professional skills with the goal of becoming an independent physician-scientist focused on advancing non-invasive testing using cell-free nucleic acids as cancer biomarkers. Essential components of the career development plan are: (1) mentorship from a multidisciplinary team of scientists and physician-scientists with expertise in advanced molecular techniques, bioinformatics, biostatistics, and clinical study design; (2) formal didactics to expand on knowledge in clinical study design, cancer biology, bioinformatics, and professional development; (3) laboratory testing and analysis of cell-free DNA as biomarkers for prostate cancer; (4) professional development in the transition to independence, and (5) data collection for an R01 application. A mentorship and multidisciplinary scientific committee has been assembled to facilitate the proposal aims and progression towards independence. This plan will be implemented at University of California, San Francisco, which provides an exceptional research environment, state-of-art facilities, and a supportive scientific community that will be an ideal environment to foster career development and project success.

项目摘要/摘要每年，美国有超过161,000名男性被诊断出患有前列腺癌。前列腺癌症仍然是癌症相关死亡率的重要原因，早期筛查工作受到了阻碍大多数案件不是致命的事实不良副作用。该提案的目的是开拓新的非侵入性诊断来区分在高风险与低风险前列腺癌之间，以指导临床管理。该提议的核心假设是拷贝数变化和甲基化标记可以是在循环核酸中无创的作为侵入性组织标记的替代物，这些标记可能会冒险分层局部前列腺癌。第一个目标将评估两个非侵入性使用下一代测序（NGS）方法的前列腺癌生物标志物。等离子体并将测试尿液样品的拷贝数变化和甲基化标记，并比较反对从前列腺手术中采取的并发前列腺癌组织。第二个目标将评估第一个目的是为了使局部前列腺癌在A 横断面研究。在K08的指导中，临床科学家研究职业发展奖应用程序，申请人WEI GU，医学博士，博士是UCSF实验室的董事会认证临床病理学家药品。该建议涵盖了一项五年计划，以增强他的研究和专业技能以成为一名独立医师 - 科学家的目标，致力于推进非侵入性使用无细胞核酸作为癌症生物标志物进行测试。职业发展计划的基本组成部分是：（1）来自多学科团队的指导具有高级分子技术，生物信息学，生物信息学专业知识的科学家和医师科学家生物统计学和临床研究设计；（2）正式的教学法扩展临床研究知识设计，癌症生物学，生物信息学和专业发展；（3）实验室测试和分析无细胞DNA作为前列腺癌的生物标志物；（4）专业发展过渡到独立性，以及（5）R01应用程序的数据收集。指导和跨学科科学委员会已组建，以促进该提案的目标向独立发展。该计划将在加利福尼亚大学SAN实施弗朗西斯科（Francisco）提供了卓越的研究环境，最先进的设施和支持性科学界将成为促进职业发展和项目的理想环境成功。