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: 8168817
• 负责人: Janet S. Rader
• 金额: $ 0.97万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168817
• 关键词: Aryl Hydrocarbon Receptor; Biological Markers; Cell Cycle; Cells; Cervical; Cervical Cancer Screening; Cervix Uteri; Collection; Computer Retrieval of Information on Scientific Projects Database; DNA damage checkpoint; Data Set; Development; Epithelial; Funding; Genes; Genomics; Grant; Institution; Liquid substance; Malignant neoplasm of cervix uteri; Methods; Microarray Analysis; Modeling; Molecular; Nucleic Acids; Outcome; Pathway interactions; Patients; Pattern; Proteins; Proteomics; Protocols documentation; Receptor Signaling; Regulation; Research; Research Personnel; Resources; Sampling; Screening procedure; Source; Specimen; Spottings; Swab; TP53 gene; Tissues; Two-Dimensional Gel Electrophoresis; United States National Institutes of Health; cDNA Arrays; cancer cell; clinical practice; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 雷德实验室有兴趣使用综合蛋白质组学和基因组学筛查来寻找宫颈癌的潜在生物标志物。宫颈癌筛查非常适合于生物标志物的开发，因为组织采集容易和组织学转变良好。此外，从子宫颈样本中获得的细胞和生物流体经历特定的分子变化，这些分子变化可以被分析和构建可以预测结果的模型。使用临床实践中已经使用的标准刮刀和细胞刷建立患者筛选蛋白质和核酸收集方案。 RNAlater用于收集样品，然后通过蛋白质组学方法鉴定在正常宫颈上皮细胞与宫颈癌细胞中差异表达的生物标志物/蛋白质。 通过二维差异凝胶电泳（2-D DIGE）鉴定了390个点，其在宫颈癌样品中以较高或较低水平（>3倍）表达。这些蛋白质组学结果进行了比较，最显着的基因在一个cDNA微阵列分析的显微切割肿瘤宫颈标本，以确定重叠的表达模式。由组合数据集代表的最常见的途径是：细胞周期：G2/M DNA损伤检查点调节;芳烃受体信号传导; p53信号传导;细胞周期：G1/S检查点调节;和内质网应激途径。