Facile screening for esophageal cancer in LMICs

中低收入国家食管癌的简便筛查

• 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
• 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

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，新增 45 万例 每年诊断的病例数和预后非常差 低成本、微创的护理点人群。 迫切需要对 ESCC 进行筛查，特别是在中低收入国家，这些国家的 ESCC 5 年生存率低于 10%。 甲基化改变经常发生在包括 EC 在内的人类恶性肿瘤中，这是一种早期事件， 可以作为早期癌症检测生物标志物然而，对于以这种方式使用DNA甲基化， 我们需要具有成本效益、用户友好且强大的测试，以允许在中低收入国家进行临床转化。 早期 ESCC 诊断策略包括使用一次性、可吞咽的海绵来收集食管标本 与智能手机操作的微流控芯片相结合，用于自动化样品处理和甲基化 该策略不需要内窥镜检查（EGD），可由医护人员进行。 没有医学学位，并且使用手机分析应用程序 海绵更便宜（大约 30 美元）。 每个），比 EGD 侵入性更小，更容易执行（总成本 1500 美元，包括设施费）； 与 EGD 不同的是，该微芯片集成了 DNA 提取、亚硫酸氢盐 DNA 转换和 此外，微芯片与手机连接，适用于两个设备。 该集成装置能够检测 DNA 甲基化。 以“样本到答案”的方式从原始样本中获取数据，无需将数据发送回分析 因此，所提出的平台为早期提供了一种经济高效且用户友好的 POC 策略。 我们还组建了一支才华横溢的跨学科团队，可在中低收入国家实施 ESCC 检测。 洲际团队执行这一战略的任务将通过以下目标分两个阶段实现： UG3 阶段：目标 1：评估样品采集、处理和甲基化的简化方案 目标2：在手机中实现DNA样本处理和甲基化检测。 目标 3：测试集成 DNA 的原型 ESCC 诊断策略。 甲基化检测系统，带有用于样本收集的可吞咽海绵 UH3 阶段： 目标 1： 提高中低收入国家使用的甲基化诊断系统的成本效益和稳健性目标 2： 开发一种环境芯片存储方法并执行芯片上 QC 测试以验证测定功能。 3：使用我们的护理点策略在乌干达进行 ESCC 诊断试验。

项目成果

Esophageal Adenocarcinoma-Derived Extracellular Vesicle MicroRNAs Induce a Neoplastic Phenotype in Gastric Organoids.

食管腺癌衍生的细胞外囊泡 MicroRNA 诱导胃类器官肿瘤表型。

• 发表时间: 2017-11
• 作者: Ke, Xiquan;Yan, Rong;Sun, Zhenguo;Cheng, Yulan;Meltzer, Amy;Lu, Nonghua;Shu, Xu;Wang, Zhe;Huang, Binbin;Liu, Xi;Wang, Zhixiong;Song, Jee Hoon;Ng, Christopher K;Ibrahim, Sariat;Abraham, John M;Shin, Eun Ji;He, Shuixiang;Meltzer, Stephen J
• 通讯作者: Meltzer, Stephen J

Determination of absolute expression profiles using multiplexed miRNA analysis.

使用多重 miRNA 分析确定绝对表达谱。

• 发表时间: 2017
• 影响因子: 3.7
• 作者: Song, Yunke;Kilburn, Duncan;Song, Jee Hoon;Cheng, Yulan;Saeui, Christopher T;Cheung, Douglas G;Croce, Carlo M;Yarema, Kevin J;Meltzer, Stephen J;Liu, Kelvin J;Wang, Tza
• 通讯作者: Wang, Tza

Epigenetic alterations of a novel antioxidant gene SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer.

新型抗氧化基因 SLC22A3 的表观遗传改变使易感个体患食道癌的风险增加。

• 发表时间: 2018
• 作者: Xiong, Ji;Wang, Yan;Sheng, Jingyi;Xiang, Di;Huang, Tu;Tan, Bin;Zeng, Cui;Li, Hua;Yang, Jiao;Meltzer, Stephen J;Mori, Yuriko;Qin, Yan;Guan, Xin;Fu, Li
• 通讯作者: Fu, Li

Gastric Cancer in the Era of Precision Medicine.

精准医学时代的胃癌。

• 发表时间: 2017-05
• 作者: Liu, Xi;Meltzer, Stephen J
• 通讯作者: Meltzer, Stephen J

A sample-to-answer droplet magnetofluidic assay platform for quantitative methylation-specific PCR.

用于定量甲基化特异性 PCR 的样本到答案液滴磁流体检测平台。

• 发表时间: 2018
• 影响因子: 2.8
• 作者: Stark, Alejandro;Shin, Dong Jin;Wang, Tza
• 通讯作者: Wang, Tza