MicroRNAs As Novel Biomarkers For Detection of Triple-Negative Breast Cancer

描述（由申请人提供）：乳腺癌是美国和全球女性中最常见的癌症。目前的筛查计划在降低乳腺癌死亡率方面并不完全成功。有一个伟大的需要继续寻找新的非侵入性生物标志物乳腺癌的检测和筛查。一个范式转变是关注识别侵袭性乳腺癌的生物标志物，而不是将所有乳腺癌混为一谈。MicroRNA代表了一类新兴的和有吸引力的癌症生物标志物，因为它们在血清和血浆中保持受保护的状态，具有组织特异性表达谱，并且可以均匀地扩增和定量。在本申请中，我们建议系统地鉴定血清中30例三阴性乳腺癌、30例其他乳腺癌和40例匹配对照之间差异表达的microRNA，然后在60例病例和40例对照的独立样本中进行复制研究。为了优先考虑和选择推定的microRNA，我们还将检查乳腺癌患者血清和乳腺组织中microRNA水平的一致性，并使用生物信息学方法和实验验证来探索它们的生物学相关性。所有生物标本均已在既往乳腺癌研究中采集。这项研究有几个创新方面，包括其系统的无偏方法，专注于侵袭性肿瘤亚型，以及使用种族多样性人群评估生物学相关miRNA的综合方法。本研究具有直接的转化作用，将为乳腺癌的预防和控制开辟新的策略。

DESCRIPTION (provided by applicant): Breast cancer is the most common cancer among women both in the United States and globally. Current screening programs are not completely successful in reducing breast cancer mortality. There is a great need to continue searching for novel non-invasive biomarkers for breast cancer detection and screening. A paradigm shift is to focus on biomarkers that identify aggressive form of breast cancer, rather than lumping all breast cancer together. MicroRNAs represent a class of emerging and attractive cancer biomarkers because they maintain in a protected state in serum and plasma, have tissue-specific expression profiles, and can be uniformly amplified and quantified. In this application, we propose to systematically identify microRNAs in serum that are differentially expressed between 30 triple-negative breast cancers, 30 other breast cancers, and 40 matched controls, followed by a replication study in an independent sample of 60 cases and 40 controls. To prioritize and select putative microRNAs, we will also examine the concordance of microRNA levels in the serum and breast tissues of breast cancer patients, and explore their biologic relevance using bioinformatics approach and experimental validation. All biospecimens have been collected in previous breast cancer studies. This study has several innovative aspects including its systematic unbiased approach, focusing on aggressive tumor subtypes, and integrated approach for assessing biological relevant miRNAs using ethnically diverse population. This study is directly translational and will open the door to new strategy of breast cancer prevention and control.