PROTEOMIC BIOMARKER PROFILING OF CERVICAL SWABS

宫颈拭子的蛋白质组生物标志物分析

• 批准号: 8361413
• 负责人: Janet S. Rader
• 金额: $ 0.81万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361413
• 关键词: Aryl Hydrocarbon Receptor; Biological Markers; Cell Cycle; Cells; Cervical; Cervical Cancer Screening; Cervix Uteri; Collection; DNA damage checkpoint; Data Set; Development; Epithelial; Funding; Genes; Genomics; Grant; Liquid substance; Malignant neoplasm of cervix uteri; Mass Spectrum Analysis; Methods; Microarray Analysis; Modeling; Molecular; National Center for Research Resources; Nucleic Acids; Outcome; Pathway interactions; Patients; Pattern; Principal Investigator; Proteins; Proteomics; Protocols documentation; Receptor Signaling; Regulation; Research; Research Infrastructure; Resources; Sampling; Screening procedure; Signal Transduction; Source; Specimen; Spottings; Swab; Tissues; Two-Dimensional Gel Electrophoresis; United States National Institutes of Health; biomedical resource; cDNA Arrays; cancer cell; clinical practice; cost; endoplasmic reticulum stress; interest; neoplastic; two-dimensional

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Rader lab is interested in using integrated proteomic and genomic screening to find potential biomarkers for cervical cancer. Cervical cancer screening is ideally suited for the development of biomarkers due to the ease of tissue acquisition and the well- established histological transitions. Furthermore, cell and biologic fluid obtained from cervix samples undergo specific molecular changes that can be profiled and models constructed that may predict outcome. A patient screening protein and nucleic acid collection protocol was established using standard spatulas and cytobrushes already used in clinical practice. RNAlater was used to collect the samples followed by proteomic methods to identify biomarkers/proteins that were differentially expressed in normal cervical epithelial versus cervical cancer cells. Three hundred ninety spots were identified via two-dimensional difference gel electrophoresis (2-D DIGE) that were expressed at either higher or lower levels (>3-fold) in cervical cancer samples. These proteomic results were compared to the most significant genes in a cDNA microarray analysis of microdissected neoplastic cervical specimens to identify overlapping patterns of expression. The most frequent pathways represented by the combined dataset were: cell cycle: G2/M DNA damage checkpoint regulation; aryl hydrocarbon receptor signaling; p53 signaling; cell cycle: G1/S checkpoint regulation; and the endoplasmic reticulum stress pathway.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 雷德实验室有兴趣使用综合蛋白质组学和基因组筛选， 宫颈癌的潜在生物标志物。宫颈癌筛查非常适合 生物标志物的发展，由于组织采集的容易性和良好的- 建立了组织学转变。此外，细胞和生物流体从 子宫颈样本经历特定的分子变化， 它可以预测结果。患者筛选蛋白质和核酸 已经建立了使用标准刮刀和细胞刷的收集方案 用于临床实践。 RNAlater用于收集样品，然后进行蛋白质组学分析。 鉴定在正常人中差异表达的生物标志物/蛋白质的方法 宫颈上皮细胞与宫颈癌细胞。 三百九十个名额， 通过二维差异凝胶电泳（2-D DIGE）鉴定， 在宫颈癌样品中以更高或更低水平（>3倍）表达。这些 将蛋白质组学结果与cDNA微阵列中最重要的基因进行比较 分析显微切割的宫颈肿瘤标本以识别重叠模式 的表达。组合数据集代表的最常见途径 细胞周期、G2/M期DNA损伤检查点调控、芳香烃受体 信号转导; p53信号转导;细胞周期：G1/S检查点调控;以及内质网 网状应激途径