Biomarkers Core

项目总结（见说明）： 生物标志物核心将为转录物的快速、高通量定量提供集中资源， proteins.将使用定量PCR（Q-PCR）对转录本进行定量。此外，生物标志物核心将提供 使用Illumina Beadstation进行全基因组微阵列分析。血液或组织中蛋白质水平的定量 将使用MesoScale Sector Imager或通过反相蛋白质阵列（RPPA）进行裂解物的生物标志物 核心将用于提供：1）参与增殖和涉及细胞增殖的已知基因的定量mRNA水平。 在癌症进展中的作用; 2）鉴定在癌症治疗后细胞或组织中的独特蛋白质、基因和表达谱， 分子或药理学操作; 3）验证最初在基因组中鉴定的基因的表达， 通过微分析筛选，4）定量蛋白水平，作为独立的验证技术， 确定转录水平和蛋白质水平之间的关系。具体目标1-4代表相互作用 在SPORE和生物标志物核心的项目之间。具体目标1用于化学预防 肥胖、胰岛素抵抗妇女的子宫内膜癌。这些研究将使用肥胖的动物模型， 进行一项使用二甲双胍的临床试验，并检查对子宫内膜癌的影响。生物标志物， 测量的包括Ki-67、细胞周期蛋白A、sFRP 1、sFRP 4、存活蛋白、EIG 121、RALDH 2、PR、ER、IGF-1、IGF-1 R。RPPA和 微阵列也将用于这些研究。具体目标2。将组织S/omarkers纳入 子宫内膜癌患者的临床管理该项目将评估一个7人小组的效用， 在大量FFPE子宫内膜样本中鉴定了生物标志物。该项目还将使用RPPA来帮助发现 新的生物标志物，以增加目前的生物标志物面板。特异性目的3 EphA 2在子宫癌中的靶向。 这些研究将评估EphA 2在癌症中的功能，并对一种新的免疫缀合物进行临床试验， 靶向EphA 2受体。Q-PCR将评估上文列出的生物标志物、血管生成的标志物和无细胞标志物。 核酸将测定活检前和活检后子宫内膜的核心生物标志物、血管生成标志物和 EphA 2转录本。将进行微阵列研究，以确定EphA 2调控的途径和新基因。 特异性目的4靶向子宫内膜癌中的Pi 3 K信号通路。在这些研究中，核心将 通过RPPA检查大约550个组织标本中的表达和磷酸化的改变， PISK信号通路的成员。具体目标5是生物标志物核心内的一个项目， 在基线时对来自HNPCC患者的约90个样品进行微阵列分析和QPCR验证， 在口服避孕药或长效甲羟孕酮进行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.