Facile screening for esophageal cancer in LMICs

中低收入国家食管癌的简便筛查

• 批准号: 9221673
• 负责人: Stephen J Meltzer
• 金额: $ 43.03万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9221673
• 关键词: 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; Esophageal Squamous Cell; Esophageal Squamous Cell Carcinoma; Esophageal Tissue; 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; Nanotechnology; Patient risk; Patients; Performance; Phase; Phonation; Polymethyl Methacrylate; Population; Porifera; 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; cancer cell; carcinogenesis; clinical translation; cost; cost effective; cost effectiveness; diagnostic accuracy; early detection biomarkers; epigenetic marker; follow-up; high risk; improved; instrument; low and middle-income countries; methylation testing; microchip; minimally invasive; mortality; noninvasive diagnosis; outcome forecast; point of care; point-of-care diagnostics; portability; prototype; sample collection; screening; superparamagnetic beads; user-friendly

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，有450,000个新的 每年诊断出的病例和预后较差。低成本，微创人群 急需筛选ESCC，尤其是在LMIC中，其中5年ESCC存活率小于10％。 甲基化改变发生在人类恶性肿瘤中，包括EC，构成了一个早期事件，该事件是 可以用作早期的癌症检测生物标志物。但是，要以这种方式使用DNA甲基化 我们需要具有成本效益，用户友好和健壮的测试，以允许LMICS进行临床翻译。我们提出了一个 ESCC的早期诊断策略完成了一次性，可吞咽的赞助商以收集食道标本 结合智能手机操纵的微流体芯片，用于自动样品处理和甲基化 检测。此策略不需要内窥镜（EGD），可以由医疗保健工人管理 没有医学学位，并使用手机分析应用程序。赞助商便宜（大约30美元 每个）比EGD（包括设施费用，包括1500美元的总费用），侵入性较低，更易于执行；没有 房间费用，与EGD不同。微芯片整合了DNA提取，甲硫酸氢盐DNA转换和 甲基化分析到单个设备中。此外，对于两个设备，微芯片与手机接口 控制和甲基化检测和分析。集成装置可以检测DNA甲基化 从“样本到撤离”方式的粗略样本中，无需将数据发送回分析 中心异地。这是提议的平台承诺早期具有成本效益且用户友好的POC策略 在LMIC中实施的ESCC检测。我们还召集了一个才华横溢的跨学科， 洲际团队执行此策略。我们的任务将通过以下目的在两个阶段中实现： UG3阶段：目标1：评估用于样本收集，加工和甲基化的简化方案 检测。目标2：将DNA样品处理和甲基化检测实施到手机中 - 操纵的微流体芯片系统。目标3：测试原型ESCC诊断策略集成DNA 甲基化检测系统，可吞咽赞助商进行样品收集。 UH3阶段：目标1： 改善用于LMIC的甲基化诊断系统的成本效益和鲁棒性。目标2： 要开发一种用于环境芯片存储的方法并执行芯片QC测试以验证测定功能。目的 3：使用我们的保健策略在乌干达进行ESCC诊断试验。