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

项目摘要/摘要 多样性补充标题：识别卵巢早期上皮性疾病的血浆微生物区系生物特征 癌症检测 在美国，每年有超过21,000名妇女被诊断出患有卵巢癌，近14,000名妇女 死于这种疾病。晚期上皮性卵巢癌(EOC)与30%的总生存率有关，但 如果早期诊断，高达90%的病例可以治愈。因此，发展非侵入性和高度 在临床环境中，特定的血液检测作为筛查方法是非常有吸引力的。研究表明， 人类微生物区系是生活在体内的微生物的集合，它藏匿在EOC肿瘤组织中， 在有疾病和没有疾病的女性之间是明显独特的。然而，还需要更多的研究来 确定这些观察到的微生物区系差异是否可以在卵巢肿瘤微环境之外检测到 并可作为早期疾病的生物标志物。最近的研究发现了非感染性微生物 从其他癌症患者的血浆中分离出来的脱氧核糖核酸(DNA)，它会产生一种 卵巢癌筛查创新的令人兴奋的机会。这项多样性补充提案的目的是 识别和验证在EOC中检测到的血浆微生物生物签名，这些签名可以推动 用于早期疾病筛查的非侵入性血液测试。这项研究采用了回溯性设计，将使用 现有的联合体生物库血浆标本包括EoC病例、非EoC实体瘤病例、良性 妇科疾病病例和对照病例。我们将用以下方法评估血浆样本的微生物特征 16S rRNA基因测序和评估最具信息量的微生物的临床敏感性和特异性 严格区分有无平等机会的情况的分类群签名。这项提议标志着 假设有利于EOC的微生物群可能在血液中早期融合的思维动态变化 并预示着卵巢癌的发生。我们相信这项创新的研究将使我们能够开发一种方法来检测 通过对血液样本进行独特的细菌DNA特征筛选，在例行的井下妇女检查中及早实施EOC， 尤其是在高危女性身上。

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.