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，有450,000个新的新癌症 病例诊断出佩里和预后较差。 急需筛选ESCC，尤其是在LMIC中，其中5年ESCC存活率小于10％。 甲基化的改变经常发生在人类恶性剂中，包括EC，构成了早期事件，即 可以用作早期癌症检测生物标志物。 我们需要具有成本效益，用户友好和强大的测试，以便在LMIC中进行清洁 早期的ESCC诊断策略，包括一次性，可吞咽的海绵来收集食管样本 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 检测该策略不需要内窥镜检查（EGD） 没有医学学位，并使用手机分析应用程序。 每个）比EGD较少，更容易执行（总费用为1500美元，倾斜的设施费用）； 与EGD不同的房间费用。 甲基化分析为单个设备，此外，微芯片与手机的接口 对照和甲基化检测和分析。 从“样本到答案”的原油样本中，无需数据回分析 中央场地。 在LMIC中可以实现的ESCC检测。 执行我们的任务的洲际团队将通过以下目的进行2个阶段： UG3阶段：目标1：评估用于采样，加工和甲基化样品的垂直线条规程 检测目标2：将DNA样品处理和甲基化检测浸入手机 操纵微流体芯片系统。 甲基化检测系统，可吞咽的海绵，用于采样。 改善用于LMIC的甲基化诊断系统的成本效益和鲁棒性。 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AIM 3：使用我们的积分保健策略在乌干达进行ESCC诊断试验。

项目成果

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.

• DOI: 10.1016/j.jcmgh.2017.02.003
• 发表时间: 2017-05
• 期刊: Cellular and molecular gastroenterology and hepatology
• 影响因子: 7.2
• 作者: Liu X;Meltzer SJ
• 通讯作者: Meltzer SJ

Droplet Magnetofluidic Assay Platform for Quantitative Methylation-Specific PCR.

用于定量甲基化特异性 PCR 的液滴磁流控检测平台。

• DOI: 10.1007/978-1-0716-1811-0_13
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Stark,Alejandro;Trick,Alexander;Pisanic2nd,ThomasR;Wang,Tza-Huei
• 通讯作者: Wang,Tza-Huei

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

• DOI: 10.7150/ijbs.28482
• 发表时间: 2018
• 期刊: International journal of biological sciences
• 影响因子: 9.2
• 作者: Xiong JX;Wang YS;Sheng J;Xiang D;Huang TX;Tan BB;Zeng CM;Li HH;Yang J;Meltzer SJ;Mori Y;Qin YR;Guan XY;Fu L
• 通讯作者: Fu L