Extracellular Vesicle Proteomic Fingerprinting of Ovarian Cancer for Early Detection with a Nanoengineered Microsystem

卵巢癌细胞外囊泡蛋白质组指纹图谱用于纳米工程微系统的早期检测

• 批准号: 10526715
• 负责人: ANDREW K. GODWIN
• 金额: $ 16.08万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10526715
• 关键词: 16S ribosomal RNA sequencing; Address; BRCA mutations; Benign; Biological Markers; Blood; Blood Circulation; Blood Screening; Blood Tests; Blood specimen; Cells; Characteristics; Classification; Clinic; Clinical; Clinical Sensitivity; Collection; Complement; DNA; Detection; Development; Development Plans; Diagnosis; Disease; Disease Progression; Early Diagnosis; Epithelial ovarian cancer; Female Genital Diseases; Fingerprint; Goals; Gynecologic; Histologic; Individual; Inherited; Investigation; Kansas; Link; Lung; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of prostate; Mammalian Oviducts; Medical center; Mentors; Methods; Microbe; Nucleic Acids; Onset of illness; Ovarian; Ovarian Serous Adenocarcinoma; Ovary; Peritoneal; Peritoneum; Phylogeny; Plasma; Procedures; Proteomics; Reporting; Reproducibility; Research; Research Personnel; Risk; Sampling; Screening for Ovarian Cancer; Screening for cancer; Screening procedure; Sensitivity and Specificity; Signal Transduction; Solid Neoplasm; Specimen; Survival Rate; Taxonomy; Testing; Thinking; Tumor Tissue; United States; Universities; Woman; base; biobank; biosignature; cancer surgery; carcinogenesis; career; career development; case control; clinically relevant; cost effective; curative treatments; design; diagnostic value; early detection biomarkers; extracellular vesicles; high risk; human microbiota; improved; innovation; melanoma; microbial; microbial signature; microbiome; microbiota; microbiota profiles; microorganism; microsystems; minimally invasive; nanoengineering; novel; ovarian neoplasm; parent grant; reproductive tract; research study; screening; therapy design; tool; tumor microenvironment

Project Summary/Abstract Diversity Supplement Title: Identification of Plasma Microbiota Biosignatures for Early Epithelial Ovarian Cancer Detection Annually over 21,000 women are diagnosed in the United States with ovarian cancer and nearly 14,000 women die of the disease. Advanced epithelial ovarian cancer (EOC) is associated with an overall survival of 30% but can be cured in up to 90% of cases if diagnosed at an early stage. Therefore, developing noninvasive and highly specific blood-based tests is highly appealing as screening methods in clinic settings. Research suggests that human microbiota, a collection of microorganisms that live in the body, are harbored in EOC tumor tissue that are distinctly unique between women with and without disease. However, additional research is needed to determine if these observed microbiota differences can be detected outside the ovarian tumor microenvironment and serve as biomarkers of early disease. Recent investigations have identified noninfectious microbial deoxyribonucleic acid (DNA) isolated in blood plasma from individuals with other cancers, which creates an exciting opportunity for ovarian cancer screening innovation. The purpose of this diversity supplement proposal is to identify and validate plasma microbial biosignatures detected in EOC that can drive the development of non-invasive blood tests for early disease screening. This study applies a retrospective design that will use existing consortium biobank plasma specimens including EOC cases, non-EOC solid tumor cases, benign gynecologic disease cases, and control cases. We will evaluate the microbial signatures of plasma samples with 16S rRNA gene sequencing and assess the clinical sensitivity and specificity of the most informative microbial taxa signature that rigorously discriminates between cases with and without EOC. This proposal marks a dynamic change in thinking to postulate that EOC-favorable microbiota may coalesce in the bloodstream early and signify ovarian carcinogenesis. We believe this innovative study will allow us to develop a method to detect early EOC during a routine well women exam by screening blood samples for unique bacterial DNA signatures, especially in women who are at high risk.

项目摘要/摘要 多样性补充标题：早期上皮卵巢的血浆微生物群生物签名的识别 癌症检测 在美国，每年有超过21,000名妇女患有卵巢癌和近14,000名妇女 死于疾病。晚期上皮卵巢癌（EOC）的总生存率为30％，但 如果在早期被诊断出，则可以在多达90％的病例中治愈。因此，发展无创和高度 作为临床环境中的筛查方法，基于血液的特定测试具有很高的吸引力。研究表明 人类微生物群是一种生活在体内的微生物的集合，在EOC肿瘤组织中藏有 患有和没有疾病的妇女之间的独特性是明显独特的。但是，需要进一步的研究 确定是否可以在卵巢肿瘤微环境之外检测到这些观察到的微生物差异 并充当早期疾病的生物标志物。最近的调查已经确定了非感染的微生物 脱氧核糖核酸（DNA）在血浆中与其他癌症的个体分离出来，这会产生 卵巢癌筛查创新的激动人心的机会。这种多样性补充提案的目的 是识别和验证EOC中检测到的血浆微生物生物签名 早期疾病筛查的非侵入性血液检查。这项研究采用了回顾性设计 现有的联盟生物库等离子体标本，包括EOC病例，非EOC实体瘤病例，良性 妇科疾病病例和控制病例。我们将评估血浆样品的微生物特征 16S rRNA基因测序并评估最有用的微生物的临床灵敏度和特异性 分类单元签名严格区分有和没有EOC的案件。该提议标志着 思维的动态变化以假设有利于EOC的微生物群可能会早期结合 并表示卵巢癌变。我们认为这项创新的研究将使我们能够开发一种检测方法 通过筛查血液样本的独特细菌DNA特征，在常规井女性检查中的早期EOC， 特别是在高风险的女性中。