Immuno-inflammatory Response Non-coding RNAs as Predictors of HPV Status & Outcome of Oropharyngeal Cancer Patients

免疫炎症反应非编码 RNA 作为 HPV 状态的预测因子

• 批准号: 10531264
• 负责人: Guojun Li
• 金额: $ 9.72万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10531264
• 关键词: Affect; Alcohols; Behavior; Bioinformatics; Biological Markers; Cancer Patient; Cell Line; Clinical; Diagnosis; Disease; Disease-Free Survival; Epidemiology; Etiology; Exhibits; Genes; Genetic Transcription; Heterogeneity; Human; Human Papillomavirus; Human papilloma virus infection; Immunologic Surveillance; In Vitro; Incidence; Individual; Infection; Inflammatory Response; Life; Malignant Neoplasms; Methods; MicroRNAs; Molecular; Morbidity - disease rate; Mutation; Oncogenes; Oncogenic; Oropharyngeal Squamous Cell Carcinoma; Outcome; Pathway interactions; Patients; Physicians; Pilot Projects; Population; Population Study; Predisposition; Prevalence; Prevention; Preventive vaccine; Prognosis; Prognostic Marker; Public Health; Quality of life; Radiation Tolerance; Radiation therapy; Risk; Serum; Smoking; Tissues; Tobacco; Tumor Markers; Tumor Suppressor Proteins; University of Texas M D Anderson Cancer Center; Untranslated RNA; Vaccination; cohort; functional outcomes; human papilloma virus oropharyngeal squamous cell carcinoma; improved; individualized medicine; interest; knock-down; malignant oropharynx neoplasm; novel; novel marker; patient biomarkers; patient prognosis; patient screening; patient stratification; personalized medicine; predictive modeling; prognostic; prognostication; recruit; reduce tobacco use; response; screening; smoking prevalence; surveillance strategy; survival prediction; treatment response; treatment strategy; trend; tumor; young adult

PROJECT SUMMARY Squamous cell carcinoma of the oropharynx (SCCOP) is a highly morbid, life-threatening disease. Despite declining smoking prevalence, the incidence of SCCOP is increasing, particularly among younger adults. This trend is the result of the rising prevalence of oncogenic human papillomavirus (HPV) infection in the population. The majority (approximately 70-80%) of SCCOP patients are HPV-positive [HPV(+)]. HPV(+) SCCOP is distinct from HPV-negative [HPV(-)] SCCOP in terms of epidemiologic, clinical, and molecular features, and especially in terms of clinical behavior, response to treatment and survival. Therefore, in patients with SCCOP, determination of HPV status is critical for defining prognosis and tailoring therapy. Unfortunately, there is currently no effective screening method to identify patients with tumor HPV(+) SCCOP. Further, among patients with HPV(+) SCCOP, there remains heterogeneity in clinical outcomes. Identification of patients with SCCOP needing treatment intensification and those able to benefit from reduction of treatment intensity is critical to more effective and less morbid treatment. Noncoding RNAs (ncRNAs) that affect the immuno-inflammatory response control HPV clearance and escape of immune surveillance, and may contribute to tumor HPV status and related clinical outcomes of SCCOP patients. NcRNAs exhibit stable expression in human serum. We hypothesize that pretreatment serum expression profiles of immuno-inflammatory response ncRNAs are associated with tumor HPV(+) SCCOP and related clinical outcomes. The specific aims for this project are as follows: Aim 1: To determine if pretreatment serum expression profiles of selected immuno-inflammatory response ncRNAs are markers of tumor HPV status in a cohort of 1500 patients with incident SCCOP recruited, treated, and followed at The University of Texas MD Anderson Cancer Center. Aim 2: To determine if pretreatment serum expression profiles of selected immuno-inflammatory response ncRNAs predict disease-specific survival, disease-free survival, and overall survival among HPV(+) SCCOP patients from the cohort described for Aim 1. Aim 3: To validate significant associations found in Aims 1 and 2. We will use an independent cohort of 625 SCCOP cases to control for potential false-positive or unbiased estimates of associations. Aim 4: To characterize functions of immuno-inflammatory response ncRNAs on tumor radiosensitivity in vitro. We will screen a panel of HPV(+) SCCOP cell lines for ncRNAs of interest in a clinical setting, in order to further validate these prognostic ncRNAs found in Aim 2. This functional study will validate 1 or more of these ncRNAs as biomarkers that can be incorporated into prognostic prediction models to permit more personalized treatment. Identifying novel biomarkers for tumor HPV status and prognosis of patients with HPV(+) SCCOP will allow physicians to more effectively tailor screening for patients at risk of HPV(+) SCCOP, as well as treatment, and surveillance strategies that optimize survival and quality of life for patients with HPV(+) SCCOP.

项目摘要 口咽（SCCOP）的鳞状细胞癌是一种高度病态的威胁生命的疾病。尽管 吸烟流行率下降，SCCOP的发生率正在增加，尤其是在年轻人中。这 趋势是人群中致癌性人乳头瘤病毒（HPV）感染的患病率上升的结果。 大多数（约70-80％）的SCCOP患者是HPV阳性[HPV（+）]。 HPV（+）SCCOP是不同的 从HPV阴性[HPV（ - ）] SCCOP，就流行病学，临床和分子特征而言，尤其是 在临床行为，对治疗和生存的反应方面。因此，在患有SCCOP的患者中 HPV状态的确定对于定义预后和调整疗法至关重要。不幸的是，有 目前尚无有效的筛查方法来鉴定患有肿瘤HPV（+）SCCOP的患者。此外，在患者中 使用HPV（+）SCCOP，临床结果中仍然存在异质性。鉴定SCCOP患者 需要加强治疗和能够从降低治疗强度中受益的治疗强度对更多的治疗强度至关重要 有效且病态较少的治疗方法。影响免疫炎症反应的非编码RNA（NCRNA） 控制HPV清除和免疫监视的逃脱，并可能导致肿瘤HPV状态及相关 SCCOP患者的临床结果。 NCRNA在人血清中表现出稳定的表达。我们假设这一点 免疫炎症反应NCRNA的预处理血清表达谱与肿瘤有关 HPV（+）SCCOP和相关的临床结果。该项目的具体目的如下：目标1： 确定选定免疫炎症反应NCRNA的预处理血清表达谱是否是 肿瘤HPV状态的标记在1500例入射SCCOP患者的队列中招募，治疗和遵循 德克萨斯大学医学博士安德森癌症中心。目标2：确定是否表达预处理血清 选定免疫炎症反应NCRNA的特征预测疾病特异性生存，无疾病 来自同类的HPV（+）SCCOP患者的生存和总生存期，描述了AIM1。AIM3：to to to 验证在目标1和2中发现的显着关联。我们将使用625个SCCOP案例的独立队列 控制潜在的假阳性或公正的关联估计。目标4：表征 免疫炎症反应NCRNA对体外肿瘤放射敏感性的NCRNA。我们将筛选一个HPV面板（+） 为了进一步验证这些预后的NCRNA 在AIM 2中发现。这项功能研究将验证1个或更多这些NCRNA作为生物标志物 纳入预后预测模型，以允许更多个性化的治疗。识别小说 HPV患者（+）SCCOP患者的肿瘤HPV状态和预后的生物标志物将使医生能够更多 有效量身定制有HPV（+）SCCOP的患者，以及治疗和监视策略 这可以优化HPV（+）SCCOP患者的生存和生活质量。