Molecular predictors of oral cancer development

描述(由申请人提供) 尽管口腔鳞状细胞癌(SCC)的管理有所改善， 令人失望的是，5年存活率仍然很低，大约为40%。 在过去几十年里。因此，这表明需要新的 改善结果的战略。一种这样的策略是更好地理解 口腔鳞状细胞癌的最早形式，在癌前阶段，具有长期目标 防止疾病向完全发展的方向发展。口腔上皮 异型增生是口腔癌最重要的危险因素；然而， 只有大约20%的上皮异常增生症患者会进展到 恶毒。目前，对于患有异型增生的个体患者，没有可靠的 生物标志物已被发现，表明进展到 口腔鳞癌。我们的长期目标是识别分子生物标记物 预测口腔鳞癌的发展。这项拟议研究的目标是 确定特定的新生物标记物的mRNA表达水平 在我们对口腔鳞癌的微阵列研究中，在常规处理的口腔活检中 并确定这些变化是否与 发展为口腔癌。核心假设是对基因的分析 特定生物标志物的表达可用于区分哪种口腔 癌前疾病会从那些不会发展为癌症的人发展成癌症。这个 拟议研究的基本原理是，通过研究口腔癌前病变， 已知哪些进展为口腔鳞状细胞癌，关键的遗传事件是必要的 对于口腔癌的发展可以成立。这一分阶段应用程序将 意义重大，因为它将提供对 口腔癌的发展，并将确定潜在的新靶点 筛查和治疗干预。在R21阶段，我们将建立一个 可靠的定量聚合酶链式反应方法检测常规加工过程中的基因表达 口腔活组织检查。具体目标1：优化实时荧光定量聚合酶链式反应 激光显微切割(LCM)常规加工过程中的基因表达分析 口腔活组织检查。具体目标2：确定对 LCM生成的RNA用于实时荧光聚合酶链式反应。在R33阶段，我们将应用以下内容 技术进行大规模的分子流行病学研究 特定的新生物标记物，在我们的口腔微阵列研究中确定 癌症，对96名口腔癌前病变患者进行了跟踪调查 几年来，在哪里知道是哪个患者患上了口腔癌 但事实并非如此。具体目标1：确定口腔癌是否与 生物标志物在LCM-口腔上皮异型增生和口腔鳞癌中的过度表达 使用实时荧光定量聚合酶链式反应。具体目标2：确定特定的生物标志物是否可以 可用于预测口腔癌前病变患者的口腔癌发展。

DESCRIPTION (provided by applicant) Despite improvements in the management of oral squamous cell carcinoma (SCC), the 5-year survival rate has remained disappointingly low, at about 40%, for the past several decades. Therefore, this indicates the need for new strategies to improve outcome. One such strategy is to better understand the earliest forms of oral SCC, in the precancerous stage, with the long-term aim of preventing the progression to fully developed disease. Oral epithelial dysplasia is the single most important risk factor for oral cancer; however, only about 20% of all patients with epithelial dysplasia will ever progress to malignancy. Presently, for the individual patient with dysplasia, no reliable biomarkers have been discovered that indicate increased risk of progression to oral SCC. Our long-term goal is to identify molecular biomarkers that will predict oral SCC development. The objectives of this proposed research are to determine the mRNA expression levels of specific novel biomarkers, identified in our microarray studies of oral SCC, in routinely processed biopsies of oral precancers and to determine if these changes are associated with the progression to oral cancer. The central hypothesis is that analysis of gene expression of specific biomarkers can be used to distinguish which oral premalignancies will progress to cancer from those which will not. The rationale for the proposed research is that by studying oral precancers, where it is known which progressed to oral SCC, critical genetic events necessary for oral cancer development can be established. This phased application will be significant because it will provide new molecular insights into the development of oral cancer and it will identify potential new targets for screening and therapeutic intervention. In the R21 phase, we will establish a reliable, quantitative PCR method for gene expression in routinely processed oral biopsies. Specific Aim 1: To optimize quantitative real-time PCR for the analysis of gene expression in laser microdissected (LCM) routinely processed oral biopsies. Specific Aim 2: To establish the quantitative requirement for LCM-generated RNA for real-time PCR. In the R33 phase, we will apply this technology to conduct a large-scale, molecular epidemiological study of specific novel biomarkers, identified in our microarray studies of oral cancer, in a cohort of 96 patients with oral precancer who have been followed for several years and where it is known which patient developed oral cancer and which did not. Specific Aim 1: To determine if oral cancer-associated biomarkers are overexpressed in LCM-oral epithelial dysplasias and oral SCC using real-time PCR. Specific Aim 2: To determine if specific biomarkers can be used to predict oral cancer development in patients with oral precancer.