Molecular Predictors of Oral Cancer Development

描述（由申请人提供） 尽管口腔鳞状细胞癌（SCC）的治疗有所改善， 5年生存率仍然很低，约为40%， 在过去的几十年里因此，这表明需要新的 改善结果的战略。其中一个策略是更好地理解 口腔鳞状细胞癌的早期形式，处于癌前阶段，长期目标是 防止疾病发展到成熟阶段口腔上皮 发育异常是口腔癌的唯一最重要的危险因素;然而， 只有大约20%的上皮发育不良患者会发展到 恶性肿瘤目前，对于发育不良的个体患者，没有可靠的 已经发现了生物标志物，其指示进展为 口腔鳞状细胞癌我们的长期目标是确定分子生物标志物， 预测口腔SCC的发展。这项拟议研究的目标是 确定特定的新生物标志物的mRNA表达水平， 在我们对口腔鳞状细胞癌的微阵列研究中，在口腔鳞状细胞癌的常规活检中， 并确定这些变化是否与 发展为口腔癌。核心假设是基因分析 特异性生物标志物的表达可用于区分哪些口腔癌是恶性的。 癌前病变将从那些不会发展为癌症的病变发展为癌症。的 这项研究的基本原理是，通过研究口腔癌前病变， 已知哪些进展为口腔SCC，关键的遗传事件是必要的， 口腔癌的发展可以建立。这一分阶段应用将 因为它将提供新的分子见解， 口腔癌的发展，它将确定潜在的新目标， 筛查和治疗干预。在R21阶段，我们将建立 可靠的定量PCR方法，用于常规处理的 口腔活检具体目标1：优化用于检测大肠杆菌的实时荧光定量PCR方法， 常规处理的激光显微切割（LCM）中的基因表达分析 口腔活检具体目标2：确定以下方面的定量要求： 用于实时PCR的LCM生成的RNA。在R33阶段，我们将应用此 技术进行大规模的，分子流行病学研究， 特异性新的生物标志物，在我们的口腔微阵列研究中鉴定， 癌症，在96例口腔癌前病变患者的队列中， 几年来，在那里知道哪个病人患上了口腔癌， 哪些没有。具体目标1：确定是否与口腔癌相关 生物标志物在LCM-口腔上皮发育不良和口腔SCC中过表达 使用实时PCR。具体目标2：确定特定生物标志物是否可以 用于预测口腔癌前期患者的口腔癌发展。

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.