Inflammatory Response miRNAs Predict HPV-associated Oropharyngeal Cancer Outcome

 描述（由申请人提供）：口咽鳞状细胞癌（SCCOP）的特征是局部肿瘤侵袭性，需要病态的局部区域治疗，生存率低，复发率高。尽管吸烟率下降，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。HPV阳性[（HPV+）] SCCOP是一种独特的流行病学、临床和分子疾病，具有潜在的独特临床行为和治疗反应。确定需要强化治疗的患者和能够从降低治疗强度中获益的患者， 有效和较少的病态治疗。HPV的致癌亚型是头颈部癌的一个独特亚群（主要是SCCOP）的关键病因。控制HPV清除和逃避免疫监视的炎症反应miRNA可能有助于HPV（+）肿瘤和SCCOP的相关结局。此外，人血清中的miRNAs在基于血清的生物标志物研究中具有巨大的潜力。因此，治疗前炎症反应miRNA的血清表达谱可能影响肿瘤HPV状态和SCCOP患者的相关结局;并且利用这种关联可能有助于开发HPV相关SCCOP患者的临床相关非肿瘤生物标志物。在本研究中，研究受试者为600例从现有头颈部鳞状细胞癌分子流行病学研究中确定的SCCOP患者。本R 03项目的具体目标是：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例SCCOP患者中肿瘤HPV状态的标志物。我们将通过使用miScript miRNA PCR阵列方法确定治疗前这些选定的miRNA的血清表达，目的2：确定治疗前上述miRNA的某些血清表达谱是否作为HPV（+）SCCOP患者临床结局的血液和非肿瘤预测因子，包括在U.T.治疗和随访的600名SCCOP患者中的疾病特异性生存期、无病生存期和总生存期。MDACC。通过了解肿瘤HPV状态并确定HPV相关SCCOP患者的新型预后生物标志物，医生可以有效地定制治疗，筛查和随访策略，以提高生存率和生活质量，并大大增强二级癌症预防。

 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.