A point-of-care salivary cytokine test for early detection of oral cancer

用于早期发现口腔癌的即时唾液细胞因子检测

• 批准号: 10760626
• 负责人: Tian Lan
• 金额: $ 26.9万
• 依托单位: GLUCOSENTIENT, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2024-08-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10760626
• 关键词: Alcohol consumption; American; Amino Acids; Annual Reports; Antibodies; Area; Areca; Asian; Attention; Biological; Biological Assay; Biological Markers; Biopsy; Blood Glucose; Cancer Patient; Case Study; Cessation of life; Clinical; Clinical Research; Collection; Complex; Consumption; Country; Data; Deglutition; Dental; Dentists; Development; Device or Instrument Development; Diagnosis; Diagnostic; Diagnostic tests; Early Diagnosis; Early Intervention; Early identification; Enzyme-Linked Immunosorbent Assay; Habits; Health; Healthcare; High Prevalence; IL8 gene; Immunoassay; Individual; Inflammatory; Interleukin-6; Laboratories; Lesion; Location; Malignant - descriptor; Malignant Neoplasms; Manuals; Mastication; Measurement; Measures; Methods; Microfluidics; Molecular Diagnostic Testing; Morbidity - disease rate; Nuts; Oral Diagnosis; Oral cavity; Outcome; Performance; Pharmaceutical Preparations; Phase; Predictive Value; Prevalence; Procedures; Prognosis; ROC Curve; Rapid screening; Renal function; Reporting; Risk; Risk Factors; Saliva; Salivary; Sampling; Sampling Biases; Screening for Oral Cancer; Sensitivity and Specificity; Site; Smoking; Specificity; Specimen; Speech; Survival Rate; System; TNF gene; Technology; Testing; Time; Tissues; Validation; Visual; assay development; cohort; cost; cytokine; design; detection limit; follow-up; glucose monitor; improved; instrument; interest; khat; large scale production; malignant mouth neoplasm; manufacturing scale-up; meter; operation; point of care; prototype; research and development; salivary assay; screening; smokeless tobacco use; success; tumor; tumorigenesis; viral DNA

Project Summary / Abstract Oral cancer is the 6th most common cancer globally with ~ 350,000 new cases and claiming ~ 180,000 lives annually. Common risk factors include smoking and alcohol consumption. However, other local habits, such as khat chewing, can cause significantly higher regional higher prevalence (up to 40% of all cancer cases in some Asian countries). Currently, identification and diagnosis of oral cancer rely on visual inspection followed by biopsy and histopathological analysis. This procedure is lengthy, costly and often prone to error. As a result, oral cancer today is often diagnosed at advanced stages that have poor prognosis with a 5-year survival rate hovering around 50% for decades. Even for those who have been cured, they often face severe morbidities, such as disfigurement, speech and swallowing difficulties. However, if oral cancer can be diagnosed early and allowing early intervention, survival rate can improve to ~ 90%. Testing for salivary biomarkers represents a promising approach for screening and diagnosing oral cancer earlier, since 1) saliva collection is convenient and can be performed even at the dentist’s office, and 2) saliva is closest to the primary site of tumor development which can contain molecules indicative of malignant transformation. Hence, with appropriate biomarkers, a simple saliva test can be developed and deployed at the point-of-care (POC, e.g., dentist’s office) for rapid screening and early identification of oral cancer. Recently, from a number of clinical studies globally, pro-inflammatory cytokines have emerged as promising biomarkers for screening and diagnosing oral cancer with good sensitivity and specificity. Among these cytokines, IL-6 and IL-8 have shown the best predictive power for oral cancer. Currently, measurement for IL-6 and IL-8, as well as other cytokines, often require tedious manual assays or delicate automated systems which can be both time consuming and costly. As a result, currently, it is impractical to screen for oral cancer via salivary biomarkers at the POC. Based on need and clinical values, GlucoSentient (GSI) is proposing to develop a POC system for screening oral cancer by measuring salivary levels of relevant pro-inflammatory cytokines. The POC system will be based on the existing blood glucose meter (BGM) hardware and a disposable microfluidic cartridge. Today’s BGM is the culmination of decades of R&D, designed POC simple operation, low cost and large-scale production. Leveraging on the BGM technology, we can significantly reduce the time and cost associated with device development and scale-up production. In this proposed Phase I project, we will demonstrate the feasibility of a POC screening test for oral cancer by developing BGM based POC tests for IL-6 and IL-8 and validate their performance in relevant specimen.

项目概要/摘要 口腔癌是全球第六大常见癌症，新增病例约 350,000 例，夺去了约 180,000 人的生命 每年。常见的危险因素包括吸烟和饮酒。然而，其他当地习惯，例如 咀嚼阿拉伯茶会导致区域患病率显着升高（在某些地区，高达所有癌症病例的 40%） 亚洲国家）。目前，口腔癌的识别和诊断依赖于目视检查和活检 和组织病理学分析。这个过程冗长、成本高并且经常容易出错。结果，口腔癌 如今，诊断时常常已处于晚期，预后较差，5 年生存率徘徊在 几十年来50%。即使对于那些已经治愈的人来说，他们也经常面临严重的疾病，例如毁容、 言语和吞咽困难。然而，如果口腔癌能够及早诊断并进行早期干预， 成活率可提高至~90%。唾液生物标志物测试代表了一种有前途的方法 早期筛查和诊断口腔癌，因为 1) 唾液采集方便，甚至可以进行 在牙医办公室，2) 唾液最接近肿瘤发展的原发部位，其中可能含有 指示恶性转化的分子。因此，利用适当的生物标志物，简单的唾液测试就可以 在护理点（POC，例如牙医办公室）开发和部署，以进行快速筛查和早期诊断 口腔癌的鉴定。 最近，从全球范围内的多项临床研究来看，促炎细胞因子已成为有前景的药物 用于筛查和诊断口腔癌的生物标志物具有良好的敏感性和特异性。在这些细胞因子中， IL-6 和 IL-8 显示出对口腔癌的最佳预测能力。目前，IL-6和IL-8的测量， 以及其他细胞因子，通常需要繁琐的手动测定或精密的自动化系统，这些系统可以 既费时又费钱。因此，目前通过唾液筛查口腔癌是不切实际的。 POC 的生物标志物。根据需求和临床价值，GlucoSentient (GSI) 提议开发 POC 通过测量相关促炎细胞因子的唾液水平来筛查口腔癌的系统。概念验证 系统将基于现有的血糖仪（BGM）硬件和一次性微流体盒。 今天的BGM是数十年研发的巅峰之作，设计的POC操作简单、成本低、规模化 生产。利用BGM技术，我们可以显着减少与BGM相关的时间和成本 设备开发和规模化生产。在这个拟议的第一阶段项目中，我们将论证可行性 通过开发基于 BGM 的 IL-6 和 IL-8 POC 测试来进行口腔癌 POC 筛查测试，并验证其结果 相关样本的性能。