Precision DNA methylation test to reduce oral cancer disparities in African Americans patients residing in low-resource settings

精密 DNA 甲基化测试可减少居住在资源匮乏地区的非裔美国人患者口腔癌的差异

• 批准号: 10706376
• 负责人: Rafael Guerrero-Preston
• 金额: $ 29.25万
• 依托单位: LIFEGENE-BIOMARKS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10706376
• 关键词: Aberrant DNA Methylation; Adult; African American; African American population; Alcohol consumption; Alcohols; Anatomy; Biological Markers; Biopsy; Black race; Businesses; Cancer Burden; Cause of Death; Chronic; Classification; Clinical; Combined Modality Therapy; DNA; DNA Methylation; DNA Sequence Alteration; Data; Dental; Detection; Developed Countries; Development; Diagnosis; Diagnostic; Disparity; Distant; Early Diagnosis; Epigenetic Process; Etiology; Evaluation; Event; Exhibits; Frequencies; Gender; Gene Expression; Gene Silencing; Genes; Genetic; Genetic Predisposition to Disease; Genomics; Head and Neck Squamous Cell Carcinoma; Hospitals; Human Papillomavirus; Hypermethylation; Incidence; Infection; Inflammation; Latino; Lesion by Stage; Link; Location; Low Income Population; Malignant Neoplasms; Metastatic Neoplasm to Lymph Nodes; Methylation; Modification; Molecular; Monitor; Mutation; Newly Diagnosed; Oncogenes; Operative Surgical Procedures; Oral Diagnosis; Oral Stage; Outcome; PAX5 gene; Patients; Performance; Preventive; Primary Neoplasm; Process; Prognosis; Prognostic Marker; Promoter Regions; Publishing; Race; Recommendation; Recording of previous events; Recurrence; Research; Resource-limited setting; Risk; Saliva; Salivary; Small Business Innovation Research Grant; Specificity; Survival Analysis; Survival Rate; TP53 gene; Technology; Testing; The Cancer Genome Atlas; Tissues; Tobacco; Tumor Cell Invasion; Tumor Promotion; Tumor Suppressor Genes; United States; Virus Diseases; Visit; advanced disease; cancer health disparity; cancer subtypes; commercialization; cost; diagnostic accuracy; early detection biomarkers; epigenomics; genetic testing; health difference; high risk; improved; low and middle-income countries; low income country; malignant mouth neoplasm; methylation biomarker; methylation testing; methylome; molecular subtypes; mouth squamous cell carcinoma; patient stratification; personalized screening; premalignant; prevent; prognostic; prognostication; promoter; risk stratification; rural area; rural patients; rurality; saliva sample; salivary assay; screening; social health determinants; tobacco control; tobacco exposure; tumor

Project Summary A diagnosis of Head and neck squamous cell carcinoma (HNSCC) includes many cancer subtypes. We will focus on the oral cavity squamous cell carcinoma (OSCC) subtype on the proposed project. OSCC is the 11th most common malignancy in the world. Despite advances in treatments, the 5-year survival rates for OSCC have not improved for the past 25 years. OSCC is a very aggressive tumor, and the majority of patients displays a locoregionally advanced disease at diagnosis, for which multimodality therapy is required. Tumor invasion, lymph node metastasis and high rates of locoregional recurrence, besides development of second primary tumors, are the leading causes of death for OSCC patients. At least 50% of patients with locally advanced OSCC develop locoregional or distant relapses, which usually occur within the first 2 years of treatment completion. Treatment in high-quality hospitals is associated with improved survival for patients with OSCC. However, African American patients are less likely to be treated in high-quality hospitals compared with non-Latino white patients in US, as well as poor patients worldwide. Most HNSCC cases worldwide are detected at later stage of cancer because screening is not routinely conducted, leading to disparities at diagnosis based on rurality, race, and gender, which can be reduced by targeted screening. OSCC is one of the tumors in which the most glaring disparities exist worldwide. The dramatic disparity in incidence rates between high- and low-income countries is due primarily to differential access to effective screening and pre- cancer, or preventive, treatment. Similar disparities also exist within developed countries like the US where the burden of OSCC is highest in low-income populations. OSCC molecular screening should be included in dental visits for adults because early detection of OSCC is associated with better survival. The development of OSCC is a multistep process requiring the accumulation of multiple DNA alterations, influenced by a patient's genetic predisposition as well as by environmental influences, including tobacco, alcohol, chronic inflammation, and infection with Human Papilloma Virus. DNA alterations consist of two major types: alterations in tumor suppressor genes, which promote tumor development when inactivated; and alterations in oncogenes, which promote tumor development when activated. Tumor suppressor genes can be inactivated through genetic events or by epigenetic modifications such as DNA methylation. Gene silencing by aberrant DNA methylation is an important epigenetic event in cancer development and progression, which has great potential as a biomarker for early diagnosis, tumor molecular subtyping, prognosis, monitoring, and therapy. In this Fast Track SBIR project, we propose to demonstrate the feasibility for the commercialization of a precision DNA methylation test, the OralMethDx Test, to stratify patients at high risk of OSCC. Our business plan is to evaluate the performance of the OralMethDx Test for two separate indications: A saliva test for risk stratification in screening and early detection; and tissue biopsy test for diagnosis and prognostication.

项目概要 头颈鳞状细胞癌 (HNSCC) 的诊断包括多种癌症亚型。我们将 拟议项目的重点是口腔鳞状细胞癌（OSCC）亚型。 OSCC是第11个 世界上最常见的恶性肿瘤。尽管治疗方法取得了进步，但 OSCC 的 5 年生存率 过去25年没有任何改善。 OSCC 是一种侵袭性很强的肿瘤，大多数患者 诊断时显示出局部晚期疾病，需要多学科治疗。瘤 侵袭、淋巴结转移和高局部区域复发率，以及第二次复发 原发性肿瘤是 OSCC 患者死亡的主要原因。至少50%的患者患有局部疾病 晚期 OSCC 会出现局部或远处复发，通常发生在治疗后的头 2 年内 治疗完成。高质量医院的治疗与患者生存率的提高有关 OSCC。然而，与其他国家相比，非裔美国患者在优质医院接受治疗的可能性较小 美国的非拉丁裔白人患者以及世界各地的贫困患者。全球大多数 HNSCC 病例是 由于筛查并未常规进行，因此在癌症晚期才被发现，导致诊断结果存在差异 基于农村地区、种族和性别的诊断，可以通过有针对性的筛查来减少。 OSCC 是其中之一 世界范围内存在最明显差异的肿瘤。发病率的巨大差异 高收入国家和低收入国家之间的差异主要是由于获得有效筛查和预检的机会存在差异。 癌症或预防性治疗。美国等发达国家也存在类似的差距 OSCC 的负担在低收入人群中最高。 OSCC 分子筛查应纳入 成人牙科就诊，因为早期发现 OSCC 与更好的生存相关。的发展 OSCC 是一个多步骤的过程，需要积累多种 DNA 改变，并受患者自身情况的影响 遗传倾向以及环境影响，包括烟草、酒精、慢性病 炎症和人乳头瘤病毒感染。 DNA 改变包括两种主要类型： 抑癌基因的改变，失活后会促进肿瘤的发展；和改变 癌基因，激活后会促进肿瘤的发展。抑癌基因可以失活 通过遗传事件或表观遗传修饰（例如 DNA 甲基化）。异常基因沉默 DNA甲基化是癌症发生、发展过程中重要的表观遗传事件，对癌症的发生发展具有重要意义。 作为早期诊断、肿瘤分子分型、预后、监测和治疗的生物标志物的潜力。在 在这个 Fast Track SBIR 项目中，我们建议展示精密技术商业化的可行性 DNA 甲基化测试（OralMethDx 测试）可对 OSCC 高风险患者进行分层。我们的商业计划是 评估 OralMethDx 测试针对两种不同适应症的性能： 唾液风险测试 筛查和早期检测分层；以及用于诊断和预测的组织活检测试。