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: 10929597
• 负责人: Shi-Long Lu
• 金额: $ 31.61万
• 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 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10929597
• 关键词: Algorithms; Applications Grants; Biological Assay; Cancer Detection; 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; Magnetic Resonance Imaging; Malignant Neoplasms; Medical; Medical Imaging; Methods; Methylation; MicroRNAs; National Comprehensive Cancer Network; Nature; Observational Study; Operative Surgical Procedures; Oral cavity; Outcome; PET/CT scan; Patients; Performance; Periodicals; Pharyngeal structure; Phase; Prevalence; Prospective Studies; Publishing; Radiation exposure; Radiation therapy; Recommendation; Recurrence; Recurrent Malignant Neoplasm; 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; 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.

项目摘要 这种UH 2/UH 3联合应用的目的是开发一种非侵入性、准确且具有成本效益的 以唾液为基础的测试，用于早期检测头颈部鳞状细胞癌（SCCHN）复发。 SCCHN包括源自口腔、舌、咽和喉的鳞状细胞癌。今天是第七天 美国和全球最常见的癌症（按发病率计算），5年时在美国排名第3，在全球排名第4 普遍性。SCCHN是一种生物学侵袭性癌症，其中复发率高（局部、局部区域或局部淋巴结转移）。 远距离）显著地导致患者存活率差。目前临床实践中检测 SCCHN复发是主观的，侵入性的，难以接近，不能及时发现复发 方式或昂贵。存在对客观的、非侵入性的、容易获得的测试的未满足的医学需求，其 能够以及时和具有成本效益的方式检测SCCHN复发。我们的解决方案是“HNKlear”，一个非- 侵入性，唾液为基础的候选测试早期检测SCCHN复发。HNKlear采用了7- 甲基化microRNA生物标志物组。我们测试的实时性将提供更及时和精确的 SCCHN复发的检测。在我们发表的概念验证研究中，HNKlear证明了92%的 在约300份SCCHN和对照组织样本中，敏感性和特异性分别为98%和85%， ~200个SCCHN和对照唾液样本使用连续变量，这支持临床翻译 考试我们提出了一个合并的UH 2/UH 3应用程序的临床翻译HNKlear。在UH 2 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锁定测试，并在达到里程碑时关闭。然后我们将进行 一项UH 3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HNKlear用于早期检测SCCHN复发的临床有效性的有力证据， 将进一步使HNKlear作为实验室开发的测试的临床应用成为可能。