MICRORNA BIOMARKERS FOR OROPHARYNGEAL CANCER

项目摘要 头颈癌是美国第五大最常见的癌症，总体上 存活率在50%左右。与头颈癌的其他亚部位相比， 口咽癌的发病率正在上升，并已与人类 乳头瘤病毒(HPV)。大多数口咽癌患者接受标准治疗。然而， 临床结果差异很大，很难预测。因此，更可靠的预测 需要生物标志物来准确地对患者治疗失败的风险进行分层。 这项研究的长期目标是开发临床预后分析和 口咽癌个体化治疗药物的研究 MicroRNA。MicroRNAs(MiRNAs)是一类非编码的小RNA分子， 共同控制着数以千计的蛋白质编码基因的表达。MiRNAs是 广泛参与肿瘤发生，并在人类癌症中解除表达调控。 最近的研究表明miRNAs是很有前景的生物标志物，并发挥着重要的调节作用。 在许多类型的癌症中。然而，miRNAs的预后和治疗价值 口咽癌到目前为止还没有得到很好的描述。我们的初步分析已经确定 预测口咽癌预后的六个miRNAs。在此，我们建议 显著扩展我们的初步研究，通过分析所有 口咽相关miRNAs在大量口咽部肿瘤中的表达。这些miRNA 然后，生物标志物将被结合起来，建立一个显著改善预后的稳健模型 口咽癌。此外，选定的预测miRNAs的治疗潜力将是 通过表征这些miRNAs在癌症进展和治疗中的作用进行评估 回应。

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.