Inflammatory Response miRNAs Predict HPV-associated Oropharyngeal Cancer Outcome

 描述(申请人提供)：口咽鳞状细胞癌(SCCOP)的特点是局部肿瘤侵袭性，需要病态的局部区域治疗，存活率低，复发率高。尽管吸烟率在下降，但SCCOP的发病率正在上升，特别是在年轻人中。这些趋势可能是由于致癌性人乳头瘤病毒(HPV)在人群中的流行率上升所致。HPV阳性[(HPV+)]SCCOP是一种独特的流行病学、临床和分子疾病，具有潜在的独特的临床行为和治疗反应。确定哪些人需要加强治疗，哪些人能够从降低治疗强度中受益，这对更多 有效且病态较少的治疗。HPV的致癌亚型是一组不同的头颈癌的关键致病因素，主要是SCCOP。炎症反应miRNAs控制着HPV的清除和免疫监视的逃避，可能与HPV(+)肿瘤及SCCOP的相关结局有关。此外，人血清中的miRNAs在基于血清的生物标志物研究中具有很大的潜力。因此，治疗前炎症反应miRNAs的血清表达谱可能影响肿瘤HPV状态和SCCOP患者的相关预后；利用这种相关性可能有助于为HPV相关的SCCOP患者开发临床相关的非肿瘤生物标记物。在这项研究中，研究对象将是从现有的头颈部鳞状细胞癌分子流行病学研究中确定的600名发生SCCOP的患者。R03项目的具体目标是：目的1：评估治疗前选定的炎症/免疫反应miRNAs的血清表达谱是否可作为600名SCCOP患者肿瘤HPV状态的标志。我们将在治疗前使用miScrip miRNA聚合酶链式反应阵列法检测选定的miRNAs的血清表达，目标2：确定治疗前上述miRNAs的某些血清表达谱是否可作为预测HPV(+)SCCOP患者临床结果的血液和非肿瘤指标，包括在德州大学MDACC治疗和随访的600名SCCOP患者的疾病特异性生存期、无病生存期和总生存期。通过了解肿瘤HPV状态并确定与HPV相关的SCCOP患者的新的预后生物标志物，医生可以有效地定制治疗、筛查和后续策略，以提高生存率和更好的生活质量，并大大加强二级癌症预防。

 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.