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Defining microRNA Signatures for Early Detection in BRCA-Mutated Ovarian Cancer

定义用于早期检测 BRCA 突变卵巢癌的 microRNA 特征

基本信息

批准号：
8883459
负责人：
Daniela M Dinulescu
金额：
$ 8.53万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2016-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8883459
关键词：
Address Biological Assay Biological Markers Cancer Patient Carcinoma in Situ Cause of Death Cells Chemoprevention Clinical Data Data Data Set Development Diagnosis Diagnostic Diagnostic Neoplasm Staging Diagnostic tests Disease Disease Progression Distal Early Diagnosis Early identification Epithelium Event Face Foundations Gene Expression Profile Genes Genomics Goals Health Heterogeneity Human Invasive Lesion Knowledge Lead Lesion Malignant Female Reproductive System Neoplasm Malignant Neoplasms Malignant neoplasm of ovary Mammalian Oviducts Messenger RNA Methods MicroRNAs Modeling Molecular Molecular Profiling Morbidity - disease rate Mus Mutate Natural History Neoplasm Metastasis Neoplasms Operative Surgical Procedures Ovarian Ovary Pathway interactions Patients Peritoneal Population Sampling Screening for Ovarian Cancer Serous Serum Site Stage at Diagnosis Staging Surface Testing The Cancer Genome Atlas Time Tissues Translations Tumor Pathology Tumor Tissue Tumor stage Untranslated RNA Variant base cancer cell cancer diagnosis cancer stem cell candidate identification design differential expression genome-wide mRNA Expression mortality mouse model nano-string novel novel strategies outcome forecast ovarian neoplasm stem stem cell niche therapy resistant tumor tumor initiation tumor progression

项目摘要

DESCRIPTION (provided by applicant): Ovarian cancer has an extremely high mortality rate due it its late stage of diagnosis. Characterizing molecular events of the early precursor lesions and the stem cell niche is a first and necessary step to generating novel strategies for early detection, chemoprevention and surgical intervention in the natural history of these neoplasms. Hence, the proposed study aims at addressing a fundamental question in ovarian tumor development which is defining the molecular signature of precursor lesions and tumor initiating cells in ovarian cancer. Towards this, we are using genome-wide approaches to determine the expression of noncoding RNAs and will further determine their expression in serum in order to evaluate them as biomarkers for early detection. This is the first time that a unique murine model of ovarian cancer is being used to comprehensively characterize the changes in miRNA expression through various stages of tumor progression. This project will make a significant impact on identifying new molecular pathways for early diagnosis, which is critical in reducing the disease mortality and chemoprevention. In summary, successful completion of the proposed study would lead not only to better early detection but also development of chemopreventative methods, which could significantly impact the current prognosis of ovarian cancer patients.

描述（由申请人提供）：卵巢癌由于其诊断的晚期阶段而具有极高的死亡率。表征早期前体病变和干细胞龛的分子事件是在这些肿瘤的自然史中产生早期检测、化学预防和手术干预的新策略的第一步也是必要的步骤。因此，拟议的研究旨在解决卵巢肿瘤发展中的一个基本问题，即定义卵巢癌中前体病变和肿瘤起始细胞的分子特征。为此，我们正在使用全基因组方法来确定非编码RNA的表达，并将进一步确定它们在血清中的表达，以评估它们作为早期检测的生物标志物。这是第一次使用独特的卵巢癌小鼠模型来全面表征肿瘤进展各个阶段的miRNA表达变化。该项目将对识别早期诊断的新分子途径产生重大影响，这对于降低疾病死亡率和化学预防至关重要。总之，成功完成拟议的研究不仅可以更好地早期检测，还可以开发化学预防方法，这可能会显着影响卵巢癌患者的当前预后。