Diagnosis of Esophageal Squamous Cell Carcinoma in Low-Income Countries

低收入国家食管鳞状细胞癌的诊断

• 批准号: 10325590
• 负责人: Daniel Gregory Lunz
• 金额: $ 40万
• 依托单位: CAPSULOMICS, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2023-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325590
• 关键词: Address; Admixture; Alcohol consumption; Algorithms; Barrett Esophagus; Biological Assay; Biological Markers; Biotechnology; Blinded; Cancer Etiology; Cessation of life; Classification; Clinical; Cohort Studies; Country; DNA; DNA Methylation; Data; Death Rate; Deglutition; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Dyspepsia; Early Diagnosis; Endoscopy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagitis; Esophagogastroduodenoscopy; Funding; Gastroesophageal reflux disease; Genes; Genomic DNA; Goals; Health; Health Care Costs; Healthcare; Incidence; Income; Infrastructure; International; Legal patent; Machine Learning; Malignant neoplasm of esophagus; Measures; Methods; Methylation; Modeling; Monte Carlo Method; Morbidity - disease rate; Non-Malignant; Patients; Peptic Ulcer; Performance; Phase; Pilot Projects; Populations at Risk; Porifera; Procedures; Quality of life; Reproducibility; Research; Risk; Sampling; Seeds; Sensitivity and Specificity; Small Business Technology Transfer Research; Specificity; Specimen; Subgroup; TAC1 gene; Tanzania; Testing; Tissue Sample; Tobacco smoking behavior; Tobacco use; Training; Universities; Validation; alcohol effect; base; biomarker panel; candidate marker; capsule; case control; cohort; cost; diagnostic assay; diagnostic biomarker; esophageal squamous cell cancer; experimental study; improved; learning classifier; low and middle-income countries; low income country; machine learning algorithm; methylation biomarker; mortality; non-smoker; novel; novel diagnostics; prognostic assays; programs; random forest; success

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.

食管鳞状细胞癌 (ESCC) 每年导致全球超过 509,000 人死亡， 其中超过 80% 的病例发生在低收入和中等收入国家 (LMIC)。 可用且负担得起，ESCC 诊断是使用已知的高侵入性且昂贵的程序进行的 然而，食管胃十二指肠镜检查（EGD，也称为上消化道内窥镜检查）。 不发达国家往往无法广泛获得 EGD；因此，迫切需要 我们开发了一种基于该策略的更简单、更安全、更便宜、更容易获得的 ESCC 诊断策略。 我们在 ESCC 患者中获得的令人兴奋的初步数据：可吞咽、可回收的海绵胶囊装置 (EsophaCap) 与敏感、特异的 DNA 甲基化生物标志物组（约翰霍普金斯大学专利申请中）和机器相结合 约翰·霍普金斯大学的一家初创公司 Capsulomics, Inc. 将把学习分类器商业化。 这种检测称为“EsoCAN”，用于 ESCC 诊断。 该项目的目标是探索非内窥镜诊断测试的可行性和开发 在中低收入国家中，这是一种更方便、更便宜、更广泛使用的 EGD 替代方案。 当应用于高危人群时，可能会显着提高生存率和生活质量。 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 对 5 个候选位点进行定量甲基化特异性 PCR (qMSP) 检测：cg20655070、SLC35F1、TAC1、 ZNF132 和 ZNF542，包括 EsophaCap 的一项试点研究，收集了 50 名食管鳞癌患者的样本， 70 个控制，目标 2，创建多变量机器学习 (ML) 诊断生物标志物模型。 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 中低收入国家 ESCC 诊断的准确性。