Validation of a saliva test using methylated microRNAs for head and neck cancer recurrence

使用甲基化 microRNA 进行唾液测试验证头颈癌复发情况

• 批准号: 10491773
• 负责人: Shi-Long Lu
• 金额: $ 9.49万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10491773
• 关键词: Algorithms; Applications Grants; Biological Assay; Clinical; Clinical Practice Guideline; Clinical Research; Detection; Development; Distant; Early Diagnosis; Follow-Up Studies; Future; Goals; Head and Neck Cancer; Head and Neck Neoplasms; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Health Care Costs; Incidence; Institution; Intervention; Laboratories; Larynx; Lead; Magnetic Resonance Imaging; Malignant Neoplasms; Medical; Medical Imaging; Methods; MicroRNAs; National Comprehensive Cancer Network; Nature; Observational Study; Operative Surgical Procedures; Oral cavity; Outcome; PET/CT scan; Patients; Performance; Periodicity; Pharyngeal structure; Phase; Positron-Emission Tomography; Prevalence; Prospective Studies; Publishing; Radiation exposure; Radiation therapy; Recurrence; Reproducibility; Research; Resource-limited setting; Roentgen Rays; Saliva; Screening for cancer; Specificity; Squamous cell carcinoma; System; Testing; Time; Tissue Sample; Tissues; Tongue; Tumor Burden; Tumor Tissue; Universities; Validation; Washington; base; biomarker development; biomarker panel; cancer biomarkers; cancer recurrence; clinical application; clinical practice; clinical translation; cohort; cost effective; detection method; experimental study; genomic locus; improved; meetings; microRNA biomarkers; patient population; preclinical study; prediction algorithm; prospective; random forest; rural area; saliva analysis; saliva sample; salivary assay; screening; success; testing access; tool; ultrasound

PROJECT SUMMARY The objective of this combined UH2/UH3 application is to develop a non-invasive, accurate, and cost-effective saliva-based test for early detection of squamous cell carcinoma of the head and neck (SCCHN) recurrence. SCCHN includes squamous cell carcinomas derived from oral cavity, tongue, pharynx and larynx. It is the 7th most common cancer in US and worldwide by incidence, and the 3rd in US and 4th worldwide by 5-year prevalence. SCCHN is a biologically aggressive cancer in which high rates of recurrence (local, locoregional or distant) contribute significantly to poor patient survival. Current clinical practice methods for detection of SCCHN recurrence are either subjective, invasive, hard to access, not able to detect recurrence in a timely manner or expensive. There is an unmet medical need for an objective, non-invasive, easy to access test that is able to detect SCCHN recurrence in a timely and a cost-effective way. Our solution is “HNKlear”, a non- invasive, saliva-based candidate test for early detection of SCCHN recurrence. HNKlear incorporates a 7- methylated microRNA biomarker panel. The real-time nature of our test will provide more timely and precise detection of SCCHN recurrence. In our published proof of concept studies, HNKlear demonstrated 92% sensitivity and 98% specificity in ~300 SCCHN and control tissue samples and 85% sensitivity and 95% in ~200 SCCHN and control saliva samples using continuous variables, which supports the clinical translation of the test. We propose a combined UH2/UH3 application for the clinical translation of HNKlear. In the UH2 phase, we will analytically validate the test and algorithm in a pre-clinical study and in a new patient cohort. Success of this phase will let us lock down the test and cut-off when the milestone is met. We will then conduct a clinical study in the UH3 phase to demonstrate the clinical validity of HNKlear for SCCHN recurrence in an observational clinical follow-up study incorporating HNKlear into current clinical practice. Success of this phase will generate robust evidence of the clinical validity of HNKlear for early detection of SCCHN recurrence, and will further enable clinical application of HNKlear as a Laboratory Developed Test.

项目概要 这种 UH2/UH3 组合应用的目标是开发一种非侵入性、准确且具有成本效益的 基于唾液的检测用于早期发现头颈部鳞状细胞癌（SCCHN）复发。 SCCHN 包括源自口腔、舌、咽和喉的鳞状细胞癌。这是第 7 次 按发病率计算，它是美国和全球最常见的癌症，按 5 年计算，在美国排名第三，在全球排名第四 流行率。 SCCHN 是一种生物侵袭性癌症，其复发率很高（局部、局部或局部） 远）会导致患者生存率下降。目前临床实践中检测方法 SCCHN 复发是主观的、侵入性的、难以接近、无法及时发现复发 方式或昂贵。对于客观、非侵入性、易于访问的测试的医疗需求尚未得到满足 能够及时且经济高效地检测 SCCHN 复发。我们的解决方案是“HNKlear”，一种非 用于早期检测 SCCHN 复发的侵入性、基于唾液的候选测试。 HNKlear 包含 7- 甲基化 microRNA 生物标志物组。我们测试的实时性将提供更加及时和准确的 检测 SCCHN 复发。在我们发布的概念验证研究中，HNKlear 证明了 92% 在约 300 个 SCCHN 和对照组织样本中具有 85% 的敏感性和 98% 的特异性，在 使用连续变量约 200 个 SCCHN 和对照唾液样本，支持临床转化 测试。我们建议将 UH2/UH3 组合应用用于 HNKlear 的临床转化。在UH2 阶段，我们将在临床前研究和新患者队列中分析验证测试和算法。 这一阶段的成功将使我们能够在达到里程碑时锁定测试和截止时间。然后我们将进行 一项 UH3 期临床研究，旨在证明 HNKlear 对 SCCHN 复发的临床有效性 将 HNKlear 纳入当前临床实践的观察性临床随访研究。本阶段的成功 将产生强有力的证据证明 HNKlear 对于早期检测 SCCHN 复发的临床有效性，并且 将进一步实现 HNKlear 作为实验室开发测试的临床应用。