MICRORNA BIOMARKERS FOR OROPHARYNGEAL CANCER

项目摘要 头颈癌是美国第五大常见癌症， 存活率在50%左右。与头颈癌的其他亚部位相比， 口咽癌发病率正在增加， 乳头瘤病毒（HPV）。大多数口咽癌患者接受标准治疗。然而，在这方面， 临床结果差异很大，难以预测。因此，更可靠的预后 需要生物标志物来准确地对患者的治疗失败风险进行分层。 这项研究的长期目标是开发临床预后分析， 用于个体化口咽癌治疗的治疗剂， microRNAs。microRNA（miRNAs）是一类非编码RNA小分子， 共同控制着成千上万的蛋白质编码基因的表达。mirna是 广泛参与肿瘤发生，并且它们在人类癌症中的表达失调。 最近的研究表明，miRNAs是一种很有前途的生物标志物，并发挥着重要的调控作用 在许多类型的癌症中。然而，miRNAs的预后和治疗价值， 口咽癌的特征至今还不清楚。我们的初步分析表明 预测口咽癌结果的六种miRNA。在此，我们建议 显著扩展了我们的初步研究，通过分析所有 口咽相关的miRNA在大量口咽肿瘤中的表达。这些miRNA 然后将生物标志物组合以建立显著改善的预后的稳健模型。 口咽癌此外，所选的预后性miRNA的治疗潜力将是潜在的。 通过表征这些miRNAs在癌症进展和治疗中的作用来评估 反应

Project Summary Head and neck cancer is the fifth most common cancer in the United States, with an overall survival rate of around 50%. Compared to other subsites of head and neck cancer, the incidence of oropharyngeal cancer is increasing and has been intimately linked to human papillomavirus (HPV). Most oropharyngeal cancer patients receive standard therapy. However, clinical outcomes vary significantly and are difficult to predict. Thus, more robust prognostic biomarkers are needed to accurately stratify patients for the risk of treatment failures. The long-term goal of this research is to develop clinical prognostic assays and therapeutic agents for individualized oropharyngeal cancer treatment by focusing on microRNAs. MicroRNAs (miRNAs) are a family of small non-coding RNA molecules that collectively control the expression of thousands of protein-coding genes. miRNAs are extensively involved in tumorigenesis and they have deregulated expression in human cancers. Recent studies indicate that miRNAs are promising biomarkers and play critical regulatory roles in many types of cancer. However, the prognostic and therapeutic values of miRNAs in oropharyngeal cancer are poorly characterized to date. Our preliminary analysis has identified six miRNAs that are predictive of oropharyngeal cancer outcome. Here, we propose to significantly expand our preliminary study to identify new miRNA biomarkers by analyzing all oropharynx-related miRNAs in a large number of oropharyngeal tumors. These miRNA biomarkers will then be combined to build a robust model for significantly improved prognosis of oropharyngeal cancer. Further, the therapeutic potential of selected prognostic miRNAs will be evaluated by characterizing the roles of these miRNAs in cancer progression and treatment response.