Diagnosis of Esophageal Squamous Cell Carcinoma in Low-Income Countries

食管鳞状细胞癌（ESCC）每年在全球造成超过509，000例死亡， 这些病例中有80%以上发生在低收入和中等收入国家。在它所在的环境中 ESCC诊断是使用已知的高度侵入性和昂贵的程序进行的， 食管胃内窥镜检查（EGD，也称为上消化道内窥镜检查）。然而， 不发达国家往往无法广泛获得环境发展;因此，迫切需要 更简单、更安全、更便宜、更容易获得的ESCC诊断策略。我们制定了一项战略， 我们在ESCC患者中获得的令人兴奋的初步数据：一种可吞咽、可回收的海绵胶囊装置（EsophaCap） 结合灵敏、特异的DNA甲基化生物标志物面板（JHU专利申请中）和机器 学习分类器。Capsulomics，Inc.，一家来自约翰霍普金斯大学的创业公司， 该测定称为“EsoCAN”，用于ESCC诊断。 本项目的目标是探索非内窥镜诊断测试的可行性和发展， 在中低收入国家，EGD是一种更方便、更便宜、更广泛使用的替代品。最终，这个测试， 当应用于高危人群时，可能会大大提高生存率和生活质量。作为初始 为了实现这一目标，我们将追求以下具体目标：目标1，分析和临床验证 5个候选基因座的定量甲基化特异性PCR（qMSP）测定：cg 20655070、SLC 35 F1、TAC 1， ZNF 132和ZNF 542，包括EsophaCap的初步研究，该研究从50名ESCC患者中收集标本， 70个对照，目标2，创建多变量机器学习（ML）诊断生物标志物模型。同相 II，我们将在更大的患者队列中进一步开发和评估我们的非内窥镜诊断测试， LMIC中ESCC诊断的准确性。

Esophageal squamous cell carcinoma (ESCC) causes more than 509,000 deaths per year worldwide, and over 80% of these cases occur in low- and middle-income countries (LMICs). In the settings where it is available and affordable, ESCC diagnosis is made using the highly invasive and expensive procedure known as esophagogastroduodenoscopy (EGD, also referred to as upper endoscopy). However, citizens of underdeveloped countries often do not have widespread access to EGD; thus, there is a pressing need for easier, safer, cheaper, more accessible ESCC diagnostic strategies. We have developed a strategy based on our exciting preliminary data in ESCC patients: a swallowable, retrievable sponge-capsule device (EsophaCap) combined with a sensitive, specific DNA methylation biomarker panel (JHU patent pending) and machine learning classifiers. Capsulomics, Inc., a startup company from Johns Hopkins University, will commercialize this assay, termed “EsoCAN,” for ESCC diagnosis. The goal of this project is to explore the feasibility and development of a non-endoscopic diagnostic test as a more convenient, inexpensive, and more widely usable alternative to EGD in LMICs. Ultimately, this test, when applied to at-risk populations, is likely to significantly improve survival and quality of life. As an initial step toward this goal, we will pursue the following Specific Aims: Aim 1, analytical and clinical validation of quantitative methylation-specific PCR (qMSP) assays for 5 candidate loci: cg20655070, SLC35F1, TAC1, ZNF132, and ZNF542, including a pilot study of EsophaCap collected specimens from 50 ESCC patients and 70 controls, and Aim 2, creation of multivariate machine learning (ML) diagnostic biomarker models. In Phase II, we will further develop and evaluate our non-endoscopic diagnostic test in a larger patient cohort for accuracy of ESCC diagnosis in LMICs.