Biomarkers Core

项目总结(见说明)： 生物标记核心将为快速、高通量量化转录本和 蛋白质。转录本将使用定量聚合酶链式反应(Q-PCR)进行定量。此外，Biomarker Core将提供 使用LLUMINA串珠站进行全基因组微阵列分析。血液或组织中蛋白质水平的量化 裂解产物将使用中尺度扇形成像仪或生物标记物反相蛋白质阵列(RPPA)完成 CORE将提供：1)与增殖相关的已知基因的定量信使核糖核酸水平 在癌症进展中；2)在细胞或组织中鉴定独特的蛋白质、基因和表达谱 分子或药物操作；3)最初在 4)蛋白质水平的量化作为一种独立的验证技术和 确定转录水平和蛋白质水平之间的关系。具体目标1-4代表互动 在孢子和生物标记核心的项目之间。特异性靶点1二甲双胍用于化学预防 肥胖、胰岛素抵抗妇女中的子宫内膜癌。这些研究将使用肥胖的动物模型和 使用二甲双胍进行临床试验，检查其对子宫内膜癌的影响。生物标记物将成为 检测指标包括Ki-67、Cyclin A、sFRPI、sFRP4、Survivin、EIG121、RALDH2、PR、ER、IGF-1、IGF-1、RPPA和 微阵列也将用于这些研究。具体目标2.组织S/标志物在人体内的应用 子宫内膜癌患者的临床处理。该项目将评估一个7人小组先前的效用 在大量FFPE子宫内膜样本中确定了生物标志物。该项目还将使用RPPA帮助发现 新的生物标记物，以加强目前的生物标记物小组。特异性靶向3EphA2在子宫癌中的靶向作用 这些研究将评估EphA2在癌症中的功能，并进行一种新型免疫结合物的临床试验 靶向EphA2受体。Q-PCR将评估上述生物标记物、血管生成标记物和无细胞标记物 核酸。检测活检前后子宫内膜的核心生物标记物、血管生成标记物和 EphA2转录本。将进行微阵列研究，以确定受EphA2调控的途径和新基因。 靶向子宫内膜癌中PI3K信号通路的特异性靶点4在这些研究中，核心将 RPPA检测约550例组织标本的表达和磷酸化变化 Pisk信号通路的成员。特定目标5是Biomarker Core内的一个项目，将执行 基因芯片分析和定量聚合酶链式反应对大约90例HNPCC患者基线和 使用口服避孕药或甲羟孕酮进行3个月的化学预防治疗后。

PROJECT SUMMARY (See instructions): The biomarker core will provide a centralized resource for the rapid, high throughput quantification of transcripts and proteins. Transcripts will be quantified using quantitative PCR (Q-PCR). In addition the Biomarker Core will provide for genome-wide microarray analysis using an lllumina Beadstation. Quantification of protein levels in blood or tissue lysates will be done using a MesoScale Sector Imager or by reverse-phase protein array (RPPA) The biomarker core will serve to provide: 1) quantitative mRNA levels for known genes that are Involved In proliferation and implicated in cancer progression; 2) identification of unique proteins, genes and expression profiles in cells or tissues after a molecular or pharmacologic manipulation; 3) validation of the expression of genes that are initially identified in screening by microan-ays, 4) quantification of protein levels both as an independent validation technique and to determine the relationship between transcript levels and protein levels. Specific Aims 1-4 represent interactions between projects in the SPORE and the Biomarker Core. Specific Aim 1 Metformin for the chemoprevention of endometrial cancer in obese, insulin resistant women. These studies will use both animal models of obesity and conduct a clinical trial using metformin and examine the impact on endometrial cancer. Biomarkers that will be measured include Ki-67, Cyclin A, sFRPI, sFRP4, survivin, EIG121, RALDH2, PR, ER, IGF-1 IGF-1 R. RPPA and microarrays will also be used in these studies. Specific Aim 2. Sfrafegy for the Incorporation of Tissue S/omarkers in the Clinicai Management of Endometrial Cancer Patients. This project will assess the utility of a panel of 7 previously identified biomarkers in a large number of FFPE endometrial samples. This project will also use RPPA to help discover new biomarkers to augment the current biomarker panel. Specific Aim 3 EphA2 Targeting in Uterine Carcinoma. These studies will evaluate the function of EphA2 in cancer and conduct a clinical trial of a novel immuno-conjugate that targets the EphA2 receptor. Q-PCR will assess the biomarkers listed above, markers of angiogenesis, and cell free nucleic acids. Pre-and post- biopsy endometrial will be assayed for the core biomarkers, markers of angiogenesis and EphA2 transcripts. Microarray studies will be conducted to identify both pathways and novel genes regulated by EphA2. Specific Aim 4 Targeting the Pi3K Signaling Pathway in Endometrial Carcinoma. In these studies the Core will examine by RPPA approximately 550 tissue specimens for alteration in the expression and phosphorylation of members of the PISK signaling pathway. Specific Aim 5 is a project within the Biomarker Core that will perform microarray analysis and QPCR validation on approximately 90 samples from patients with HNPCC at baseline and following 3 months of chemoprevention therapy with either oral contraceptives or depot medroxyprogesterone.