MicroRNA in Blood as an Early Biomarker of Breast Cancer

血液中的 MicroRNA 作为乳腺癌的早期生物标志物

• 批准号: 8228006
• 负责人: Regina M Santella
• 金额: $ 8万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8228006
• 关键词: 3' Untranslated Regions; Academic Medical Centers; Age; Australia; Authorization documentation; Biological Assay; Biological Markers; Blood; Breast Cancer Detection; Breast Cancer Early Detection; Canada; Cancer Etiology; Carcinoembryonic Antigen; Cessation of life; Collection; Consent; Data; Development; Diagnosis; Early Diagnosis; Ethnic Origin; Family-Based Registry; Funding; Future; Gene Expression; Genome; Goals; Herbert Irving Comprehensive Cancer Center; Individual; International; Laboratories; Lead; Length; Leukocytes; Malignant Neoplasms; Mammary Neoplasms; Mammography; Measurement; Messenger RNA; Methods; MicroRNAs; Molecular Profiling; Newly Diagnosed; Normal tissue morphology; Nucleotides; Oncogenes; Paraffin; Participant; Patients; Phase; Pilot Projects; Plasma; Population; Prevalence; Prospective Studies; RNA Binding; Registries; Resource Sharing; Resources; Reverse Transcription; Sampling; Screening procedure; Sensitivity and Specificity; Site; Skin Carcinoma; Specificity; Specimen; Testing; Time; Tissues; Translations; Tumor Markers; Tumor Suppressor Proteins; United States National Institutes of Health; Untranslated RNA; Validation; Woman; breast cancer family registry; cancer cell; cancer diagnosis; case control; genome-wide; high risk; malignant breast neoplasm; molecular pathology; mortality; novel; overexpression; public health relevance; tumor; tumorigenesis; young woman

DESCRIPTION (provided by applicant): Breast cancer is the most frequently diagnosed cancer in U.S. women, excluding nonmelanoma skin cancers. While mammography use has enhanced breast cancer survival, better methods are needed for screening for early detection, especially in younger women. Analysis of blood for circulating tumor markers may be useful in breast cancer screening. MicroRNAs (miR) are small (22-25 nucleotides in length) noncoding RNAs that can effectively reduce the translation of target messenger RNAs by binding to their 3' untranslated region (UTR). miRs have been proposed to contribute to oncogenesis because they can function either as tumor suppressors or oncogenes. Abnormal levels of expression for mature and/or precursor miR sequences compared with the corresponding normal tissues have been observed. Other studies have demonstrated that miRs can be found in the blood and are highly stable. These results have lead to the hypothesis that plasma levels of miRs might be useful for early diagnosis of cancer. This proposal seeks to obtain pilot funding to identify candidate biomarker miRs overexpressed in plasma of breast cancer cases compared to controls and to establish the laboratory assays for their quantitation in plasma. Breast tumor, adjacent tissues, and the corresponding bloods are available from consenting, newly-diagnosed breast cancer cases seen at Columbia University Medical Center. These resources will enable us to identify plasma miRs as promising novel biomarkers for early detection of breast cancer. There are two specific aims. Aim 1 will compare whole genome miR expression profiles in 20 plasma samples from breast cancer cases and 20 age- and ethnicity-matched controls. The top 5-10 miRs overexpressed in cases will then be assayed using a real time quantitative PCR (RT-qPCR) assay to confirm the array data and then paraffin section breast tumor/paired adjacent tissues will be analyzed to determine if they are also overexpressed in tumor compared with adjacent tissues. In Aim 2 the RT-qPCRs will be used to confirm case/control plasma differences using an independent set of 100 cases and matched controls. This pilot study will provide the resources to select breast cancer-specific miRs, establish the laboratory assays for quantitation of miRs in plasma, and demonstrate that we can detect breast cancer at the time of diagnosis. Our long term goal is to use bloods collected from participants in the Breast Cancer Family Registry, an international registry of families at high risk for breast cancer in which bloods are available prior to diagnosis. The development of screening methods for the early detection of breast cancer in high risk populations will lead to better treatment and survival. PUBLIC HEALTH RELEVANCE: This pilot study will identify miRs upregulated in plasma of breast cancer cases compared to controls that can potentially be used to screen for early diagnosis of breast cancer. The development of real time assays for their measurement in plasma and pilot data on breast cancer cases and controls will be essential for future funding of a large prospective study.

描述（由申请人提供）：乳腺癌是美国女性最常见的癌症，不包括非甲状腺瘤皮肤癌。虽然使用乳腺X线摄影的生存增强了，但需要更好的筛查以进行早期检测，尤其是在年轻女性中。循环肿瘤标记物的血液分析可能对乳腺癌筛查有用。 microRNA（miR）是小的（长度为22-25个核苷酸）非编码RNA，可以通过结合其3'未翻译区域（UTR）来有效地减少目标信使RNA的翻译。已经提出MIR会导致肿瘤发生，因为它们可以用作肿瘤抑制因子或致癌基因。与相应的正常组织相比，已经观察到成熟和/或前体miR序列的异常表达水平。其他研究表明，可以在血液中发现miR，并且高度稳定。这些结果导致了以下假设：MIR的血浆水平可能有助于早期诊断癌症。该提案旨在获得试点资金，以确定与对照组相比，在乳腺癌病例的血浆中过表达的候选生物标志物miR，并建立了在血浆中定量的实验室测定。乳腺肿瘤，邻近组织和相应的血液可通过在哥伦比亚大学医学中心看到的同意，新诊断的乳腺癌病例获得。这些资源将使我们能够将血浆miRs识别为有前途的新生物标志物，以早期检测乳腺癌。有两个具体的目标。 AIM 1将比较来自乳腺癌病例和20个年龄和种族匹配对照的20个血浆样品中的整个基因组miR表达谱。然后，将使用实时定量PCR（RT-QPCR）测定法测定过度表达的前5-10个MIR，以确认阵列数据，然后分析石蜡乳腺肿瘤/配对相邻组织，以确定与相邻组织相比在肿瘤中是否也过表达它们。在AIM 2中，RT-QPCR将用于使用独立的100个病例和匹配的对照组确认案例/控制等离子体差异。这项试验研究将提供选择乳腺癌特异性miR的资源，建立实验室在血浆中定量MIR，并证明我们可以在诊断时检测到乳腺癌。我们的长期目标是使用从乳腺癌家庭注册表中收集的血液，这是一个国际乳腺癌的家庭注册处，在诊断前可以使用血液。在高风险种群中早期发现乳腺癌的筛查方法的发展将导致更好的治疗和生存。 公共卫生相关性：与可能用于筛查乳腺癌早期诊断的对照组相比，这项试点研究将确定乳腺癌病例血浆中上调的miR。在血浆中测量的实时测定和有关乳腺癌病例和对照的试验数据的开发对于将来对一项大型前瞻性研究的资助至关重要。