Diagnosis of Esophageal Squamous Cell Carcinoma in Low-Income Countries

全球每年有超过509,000人死于食道鳞状细胞癌。 其中80%以上的病例发生在低收入和中等收入国家。在它所在的设置中 食道鳞状细胞癌的诊断是使用高侵入性和昂贵的已知程序进行的 作为食道胃十二指肠镜(EGD，也称为上内窥镜)。然而， 不发达国家往往不能广泛获得绿色发展；因此，迫切需要 更容易、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，其基础是 我们在ESCC患者中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、特定的DNA甲基化生物标志物面板(JHU正在申请专利)和机器 学习量词。来自约翰·霍普金斯大学的初创公司Capsulology，Inc.将把 这项检测被称为“EsoCAN”，用于ESCC的诊断。 本项目的目标是探索非内窥镜诊断试验AS的可行性和发展。 在LMIC中替代EGD的一种更方便、更便宜、更广泛使用的替代方案。最终，这项测试， 当应用于高危人群时，可能会显著提高存活率和生活质量。作为首字母 迈向这一目标，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：cg20655070、SLC35F1、TAC1、 ZNF132和ZNF542，包括对EsophaCap的试点研究，该研究收集了50名ESCC患者和 70个对照和目标2，创建多变量机器学习(ML)诊断生物标记物模型。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 食管鳞癌诊断的准确性。

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.