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。目前的筛查项目在降低乳腺癌死亡率方面并没有完全成功。有必要继续寻找新的非侵入性生物标志物用于乳腺癌的检测和筛查。一种模式的转变是将重点放在识别侵袭性乳腺癌的生物标志物上，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保护状态，具有组织特异性表达谱，并且可以均匀扩增和量化。在本应用中，我们建议系统地鉴定30例三阴性乳腺癌、30例其他乳腺癌和40例匹配对照之间血清中差异表达的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可能的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，并利用生物信息学方法和实验验证探索其生物学相关性。所有的生物标本都是在以前的乳腺癌研究中收集的。这项研究有几个创新的方面，包括其系统的无偏倚方法，专注于侵袭性肿瘤亚型，以及使用不同种族人群评估生物学相关mirna的综合方法。这项研究具有直接的转化意义，将为乳腺癌预防和控制的新策略打开大门。

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. PUBLIC HEALTH RELEVANCE: Breast cancer is the most common cancer among women and it is now widely accepted that breast cancer consists of several "subtypes" with triple-negative breast cancers having the worst clinical outcomes and being difficult to be detected using current screening methods. We propose to measure a class of small RNAs (microRNA) in blood of triple-negative breast cancer patients, other breast cancer patients, and healthy controls. Our long-term goal is to identify novel biomarkers for detection and screening breast cancer, especially triple-negative breast cancer.