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Facile screening for esophageal cancer in LMICs

中低收入国家食管癌的简便筛查

基本信息

批准号：
10238011
负责人：
Stephen J Meltzer
金额：
$ 93.63万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10238011
关键词：
Aberrant DNA Methylation Back Benign Biological Assay Biological Markers Car Phone Cells Cellular Phone Cessation of life ChIP-on-chip Charge Clinic Clinical Cold Chains Community Health Coupled Cytology DNA DNA Methylation Data Defect Deglutition Deposition Detection Devices Diagnosis Diagnostic Diagnostic Trial Early Diagnosis Electromagnetics Endoscopy Esophageal Squamous Cell Carcinoma Esophageal Tissue Esophagus Event Feedback Fees Freeze Drying Gold Guidelines Health Personnel Human Hypermethylation Image Intervention Lesion Liquid substance Malignant Neoplasms Malignant neoplasm of esophagus Measurement Mediating Medical Methods Methylation Microfluidic Microchips Mucous Membrane Nanotechnology Patients Performance Phase Polymethyl Methacrylate Population Porifera Prognosis Protocols documentation Quality Control Reagent Rehydrations Resources Sampling Screening for cancer Sensitivity and Specificity Services Silicon Dioxide Site Specimen System Talents Telephone Testing Time Tube Uganda Universities Validation advanced disease base bisulfite carcinogenesis clinical translation cost cost effective cost effectiveness detection platform diagnostic accuracy diagnostic platform early detection biomarkers epigenetic marker esophageal squamous cell cancer follow-up high risk improved instrument isothermal amplification low and middle-income countries methylation testing microchip minimally invasive mortality noninvasive diagnosis point of care point-of-care diagnostics portability printed circuit board prototype sample collection screening superparamagnetic beads user-friendly

项目摘要

Esophageal squamous cell carcinoma (ESCC) ranks sixth among all cancers worldwide, with 450,000 new cases diagnosed per year and a very poor prognosis. Low-cost, minimally invasive point-of-care population screening for ESCC is badly needed, particularly in LMICs, where 5-year ESCC survival is less than 10%. Altered methylation occurs frequently in human malignancies, including EC, constituting an early event that can serve as an early cancer detection biomarker. However, for DNA methylation to be used in this manner, we need cost-effective, user-friendly and robust tests that permit clinical translation in LMICs. We propose an early ESCC diagnostic strategy comprising a single-use, swallowable sponge to collect esophageal specimens coupled with a smartphone-manipulated microfluidic chip for automated sample processing and methylation detection. This strategy does not require endoscopy (EGD), can be administered by healthcare workers without medical degrees, and uses an on-phone analytic app. The sponge is cheaper (approximately $30 each), less invasive, and easier to perform than EGD ($1500 total cost, including facility fees); there are no room charges, unlike EGD. The microchip integrates DNA extraction, bisulfite DNA conversion, and methylation analysis into a single device. In addition, the microchip interfaces with a cellphone, for both device control and methylation detection and analysis. The integrated device enables detection of DNA methylation from crude samples in a “sample-to-answer” manner, without the need for sending data back to an analytic center off-site. Thus, the proposed platform promises a cost-effective and user-friendly POC strategy for early ESCC detection that is implementable in LMICs. We have also assembled a talented interdisciplinary, intercontinental team to execute this strategy. Our task will be achieved in 2 phases via the following Aims: UG3 PHASE: Aim 1: To assess a streamlined protocol for sample collection, processing and methylation detection. Aim 2: To implement DNA sample processing and methylation detection into a mobile phone- manipulated microfluidic chip system. Aim 3: To test a prototype ESCC diagnostic strategy integrating the DNA methylation detection system with the swallowable sponge for sample collection. UH3 PHASE: Aim 1: To improve the cost-effectiveness and robustness of the methylation diagnostic system for use in LMICs. Aim 2: To develop a method for ambient chip storage and perform on-chip QC tests to verify assay functionality. Aim 3: To conduct an ESCC diagnostic trial in Uganda using our point-of-care strategy.

食管鳞状细胞癌（ESCC）在全球所有癌症中排名第六，每年确诊的病例数和预后极差。低成本、微创护理点人群特别是在5年ESCC存活率低于10%的中低收入国家，迫切需要ESCC的筛查。改变的甲基化经常发生在人类恶性肿瘤中，包括EC，构成了早期事件，可以作为早期癌症检测的生物标志物。然而，对于以这种方式使用的DNA甲基化，我们需要具有成本效益、用户友好和可靠的测试，以允许在LMIC中进行临床转化。我们提出了一个早期ESCC诊断策略，包括一次性可吞咽海绵以收集食管标本再加上智能手机操控的微流控芯片，用于自动化样品处理和甲基化，侦测该策略不需要内窥镜检查（EGD），可由医护人员管理没有医学学位，使用手机分析应用程序。海绵更便宜（约30美元每个），侵入性更小，比EGD更容易执行（总费用为1500美元，包括设施费）;没有不像EGD的房间收费。微芯片集成了DNA提取，亚硫酸氢盐DNA转化，甲基化分析到单个装置中。此外，对于这两种设备来说，微芯片都与手机接口对照和甲基化检测和分析。该集成设备能够检测DNA甲基化以“样品到答案”的方式从原始样品中提取，而无需将数据发送回分析仪。中心外。因此，拟议的平台有望为早期的在LMIC中可实施的ESCC检测。我们还召集了一位才华横溢的跨学科专家，洲际团队来执行这一战略。我们的任务将通过以下目标分两个阶段实现： UG 3阶段：目标1：评估样本采集、处理和甲基化的简化方案侦测目标2：在移动的电话中实现DNA样本处理和甲基化检测- 微流控芯片系统目的3：测试整合DNA的ESCC诊断策略原型甲基化检测系统与可吞咽的海绵样品收集。UH 3阶段：目标1：提高用于LMIC的甲基化诊断系统的成本效益和稳健性。目标二：开发芯片室温储存方法，并进行芯片上QC测试，以验证检测试剂盒功能。目的 3：使用我们的即时护理策略在乌干达进行ESCC诊断试验。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement.

DOI：
10.1002/cncr.30837
发表时间：
2017-10-15
期刊：
Cancer
影响因子：
6.2
作者：
Wang Z;Cheng Y;Abraham JM;Yan R;Liu X;Chen W;Ibrahim S;Schroth GP;Ke X;He Y;Meltzer SJ
通讯作者：
Meltzer SJ

Determination of absolute expression profiles using multiplexed miRNA analysis.

DOI：
10.1371/journal.pone.0180988
发表时间：
2017
期刊：
PloS one
影响因子：
3.7
作者：
Song Y;Kilburn D;Song JH;Cheng Y;Saeui CT;Cheung DG;Croce CM;Yarema KJ;Meltzer SJ;Liu KJ;Wang TH
通讯作者：
Wang TH

Gastric Cancer in the Era of Precision Medicine.