Inflammatory Response miRNAs Predict HPV-associated Oropharyngeal Cancer Outcome

炎症反应 miRNA 预测 HPV 相关口咽癌的结果

• 批准号: 8896183
• 负责人: Guojun Li
• 金额: $ 8.21万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8896183
• 关键词: Accounting; Affect; Alcohols; Biological Markers; Blood; Cancer Center; Clinical; Clinical Data; Data; Diagnosis; Disease; Disease-Free Survival; Epidemiologic Studies; Epidemiology; Etiology; Funding; Future; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Hereditary Disease; Human; Human Papillomavirus; Human papilloma virus infection; Imaging Techniques; Immune; Immune response; Immunologic Surveillance; Incidence; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Knowledge; Malignant Neoplasms; Methods; MicroRNAs; Molecular; Molecular Profiling; Mutation; Oncogenic; Oropharyngeal Squamous Cell Carcinoma; Outcome; Pathologic Processes; Pathway interactions; Patients; Physicians; Physiological Processes; Pilot Projects; Play; Population; Prevalence; Prevention; Preventive Medicine; Prognostic Marker; Public Health; Quality of life; Radiation therapy; Recruitment Activity; Recurrence; Reporting; Research; Sampling; Secondary Cancer Prevention; Serum; Smoking; Staging; Stratification; Study Subject; Subgroup; Testing; Tissues; Tobacco; Tobacco use; Translational Repression; Tumor Markers; University of Texas M D Anderson Cancer Center; Untranslated RNA; base; behavioral response; clinical predictors; clinically relevant; cohort; epidemiologic data; follow-up; improved; individualized medicine; mRNA Transcript Degradation; malignant oropharynx neoplasm; miRNA expression profiling; novel; outcome forecast; personalized medicine; prognostic; public health relevance; radiation response; response; screening; smoking prevalence; treatment response; trend; tumor; young adult

 DESCRIPTION (provided by applicant): Squamous cell carcinoma of the oropharynx (SCCOP) is characterized by local tumor aggressiveness requiring morbid local-regional therapies with poor survival and high recurrence rates. Despite declining smoking prevalence, the incidence of SCCOP is increasing, particularly in young adults. These trends may be due to the rising prevalence of oncogenic human papillomavirus (HPV) in the population. HPV-positive [(HPV+)] SCCOP is a distinct epidemiologic, clinical, and molecular disease with potentially unique clinical behavior and treatment responses. Identification of those needing treatment intensification and those able to benefit from reduction of treatment intensity is critical to more effective and less morbid treatment. Oncogenic subtypes of HPV are critical etiologic factors in a distinct subset of head and neck cancers, chiefly SCCOP. Inflammatory response miRNAs which control the HPV clearance and escape of immune surveillance may contribute to HPV(+) tumors and related outcomes of SCCOP. In addition, miRNAs in human serum hold a great potential for serum-based biomarker research. Thus, serum expression profiles of inflammatory response miRNAs before treatment may affect tumor HPV status and related outcomes of SCCOP patients; and exploitation of such associations may help develop clinically relevant non-tumor-based biomarkers for HPV- associated SCCOP patients. In this study, the study subjects will be 600 patients with incident SCCOP identified from an existing molecular epidemiologic study of squamous cell carcinoma of the head and neck. The specific aims for this R03 project are: Aim 1: To assess if serum expression profiles of selected inflammatory/immune response miRNAs before treatment are markers of tumor HPV status among the 600 SCCOP patients. We will determine serum expression of those selected miRNAs before treatment by using the miScript miRNA PCR arrays method and Aim 2: To determine if certain serum expression profiles of above miRNAs before treatment as blood-based and non-tumor predictors of clinical outcomes of HPV(+) SCCOP patients including disease-specific survival, disease-free survival, and overall survival among 600 SCCOP patients treated and followed at U.T. MDACC. By knowing the tumor HPV status and identifying novel prognostic biomarkers of HPV-associated SCCOP patients, physicians can effectively tailor treatment, screening, and follow-up strategies for an improved survival and a better quality of life as well as greatly enhanced secondary cancer prevention.

 描述（由适用提供）：口咽（SCCOP）的鳞状细胞癌的特征是局部肿瘤侵袭性，需要病态的局部区域疗法，生存率差和复发率很高。尽管吸烟患病率下降，但SCCOP的发病率正在增加，尤其是在年轻人中。这些趋势可能是由于人群中致癌性人乳头瘤病毒（HPV）的患病率上升所致。 HPV阳性[（HPV+）] SCCOP是一种独特的流行病学，临床和分子疾病，具有潜在独特的临床行为和治疗反应。确定需要治疗加强和能够从降低治疗强度中受益的人对更多人至关重要 有效且病态较少的治疗方法。 HPV的致癌亚型是头颈癌（主要是SCCOP）不同子集中的关键病因学因素。控制HPV清除和免疫监视的逃脱的炎症反应miRNA可能有助于HPV（+）肿瘤及其相关结果。此外，人血清中的miRNA具有基于血清的生物标志物研究的巨大潜力。这就是治疗前炎症反应miRNA的血清表达谱可能会影响SCCOP患者的肿瘤HPV状态和相关结果。对这种关联的开发可能有助于开发针对HPV相关SCCOP患者的临床相关的非肿瘤生物标志物。在这项研究中，该研究受试者将是600例患有SCCOP的患者，这些患者是从头部和颈部鳞状细胞癌的现有分子流行病学研究中鉴定出的。该R03项目的具体目的是：目标1：评估治疗前选定的炎症/免疫反应miRNA的血清表达谱是否是600名SCCOP患者肿瘤HPV状态的标志。我们将通过使用歧义miRNA PCR阵列方法来确定那些选定的miRNA的血清表达，并旨在确定上述miRNA的某些血清表达特征是否作为血液基于血液和非肿瘤预测因素和非肿瘤预测指标，包括HPV（+）SCCOP患者的临床结局，包括疾病特异性患者，包括疾病生存，疾病生存，以及600 ccc ewert ewart，以及在600 ccc pretial corne tore tore。 MDACC。通过了解肿瘤HPV状态并确定与HPV相关的SCCOP患者的新型预后生物标志物，医生可以有效地量身定制治疗，筛查和后续策略，以改善生存率和更好的生活质量，并大大增强二级癌症的预防。