PA-21-071 for Pathea Bruno to CA260126-01 Identifying a proteomic signature for breast cancer detection in breast milk and serum

PA-21-071 用于 Pathea Bruno 至 CA260126-01 鉴定用于母乳和血清中乳腺癌检测的蛋白质组学特征

• 批准号: 10597843
• 负责人: Costel C. Darie
• 金额: $ 16.38万
• 依托单位: CLARKSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-22 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10597843
• 关键词: Address; Age; Area; Biochemical; Biochemical Pathway; Bioinformatics; Biological Markers; Blood; Breast; Breast Cancer Detection; Breast Cancer Prevention; Breast Cancer Risk Factor; Caseins; Chromatography; Collection; Complement; Development; Diagnosis; Diagnostic; Early Diagnosis; Early Intervention; Early treatment; Environment; Fatty-acid synthase; Funding; Glycoproteins; Goals; Grant; Growth; Health; Human Milk; Individual; Lactate Dehydrogenase; Lactoferrin; Lead; Lipase; Malignant Neoplasms; Mass Spectrum Analysis; Measures; Medical Research; Methods; Milk; Milk Proteins; Outcome; Oxidases; Pathway interactions; Population; Premenopause; Preventive treatment; Primary Prevention; Principal Investigator; Process; Proteins; Proteomics; Research; Risk; Role; Sampling; Serum; Serum Proteins; Set protein; Source; Specialist; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Training; Translations; Woman; Women' s Group; XDH gene; base; bile salts; biomarker signature; breast cancer progression; career; ductal breast carcinoma; epidemiology study; experimental study; infiltrating duct carcinoma; malignant breast neoplasm; mass spectrometer; mortality; multiple reaction monitoring; parent grant; programs; proteomic signature; public health relevance; reproductive; tandem mass spectrometry; tool; undergraduate student; young woman

Program Director/Principal Investigator (Last, First, Middle): Darie, Costel C. Supplement Application (PAR-18-714) for Candidate Pathea Bruno Funded parent grant CA260126-01: Identifying a proteomic signature for breast cancer detection in breast milk and serum. Project summary Breast Cancer (BC) in young women (reproductive age, pre-menopausal) is associated with increased mortality, and current methods of detecting BC in this group of women have known limitations. Tools for accurately assessing personal BC risk in young women are needed to identify the women who will benefit the most from earlier intervention. Breast milk provides a noninvasive way to examine the health of the breast. We will apply quantitative proteomics to a unique collection of breast milk samples to determine if there is a group of proteins (proteomic signature) that can be used to detect early breast cancer and predict which women are at increased risk of developing BC. We hypothesize that a set of proteins exist in breast milk that can be used to identify women with BC and women at increased risk of developing BC at a young age. We also hypothesize that the set of proteins, detected in the breast milk, can also be detected in the blood and be used to detect BC in non-lactating women. We will identify and quantify proteomics BC signatures in breastmilk and serum that are both potential diagnostics and also inform on pathways and processes that are dysregulated in BC. In Aim 1, we will employ a Multiple Reaction Monitoring (MRM) approach to develop a quantitation method and then use it to quantify the proteins in the milk (20 vs 20) and serum (50 vs 50) samples of donors with Invasive Ductal Carcinoma (IDC) and matched controls, which were already identified as dysregulated by our lab or in other studies. In Aim 2, we will perform peptidomics analysis of the same milk and serum samples. We will analyze them by 1) nanoliquid chromatography tandem mass spectrometry (nanoLC-MS/MS) and 2) by Matrix Assisted Laser Desorption Ionization mass spectrometry (MALDI-MS). These two methods complement each other. In Aim 3, we will use bioinformatics approaches to investigate both the function of the dysregulated milk & serum proteins and their role in onset and progression of BC. The unique aspects of our study include proteomics analysis of breast milk for assessing BC risk. Translation of the proteomic signature from a local microenvironment (breasts) to a systemic environment (blood) will then allow its use in the detection of BC in non-lactating women. Our proposal can impact several medical and research areas: 1) to prevent BC (primary prevention), 2) to identify what makes the breast susceptible to cancer development, and 3) to identify the biochemical pathways that facilitate BC growth, leading to preventive treatments. This AREA grant will also train an extensive number of undergraduate students and direct them towards careers in biomedical fields. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

项目负责人/主要研究者（最后，第一，中间）：Darie，Costel C. 候选人Pathea Bruno的补充申请（PAR-18-714） CA 260126 -01：确定乳腺癌检测的蛋白质组特征 牛奶和血清。 项目摘要 年轻女性（育龄，绝经前）的乳腺癌（BC）与增加的 死亡率，目前检测这组妇女中BC的方法具有已知的局限性。工具 需要准确评估年轻女性的个人BC风险，以确定哪些女性将受益于 大部分来自早期干预。母乳提供了一种非侵入性的方式来检查乳房的健康。我们 将定量蛋白质组学应用于一组独特的母乳样本，以确定是否存在一组 蛋白质（蛋白质组学特征）可用于检测早期乳腺癌并预测哪些女性是乳腺癌患者。 患BC的风险增加。我们假设母乳中存在一组蛋白质， 确定患有BC的妇女和年轻时患BC风险增加的妇女。我们还假设 在母乳中检测到的这组蛋白质也可以在血液中检测到并用于检测BC 在非哺乳期妇女中。我们将鉴定和量化母乳和血清中的蛋白质组学BC特征 这既是潜在的诊断方法，也能为失调的途径和过程提供信息， 在BC。在目标1中，我们将采用多反应监测（MRM）方法来开发定量 方法，然后用它来定量的蛋白质在牛奶（20对20）和血清（50对50）样本的捐助者 与浸润性导管癌（IDC）和匹配的对照，这已经被确定为失调， 我们的实验室或其他研究中。在目标2中，我们将对相同的乳汁和血清样品进行肽组学分析。 我们将通过1）纳米液相色谱串联质谱法（nanoLC-MS/MS）和2） 基质辅助激光解吸电离质谱（MALDI-MS）。这两种方法相辅相成 对方.在目标3中，我们将使用生物信息学方法来研究失调的蛋白质的功能， 牛奶和血清蛋白及其在BC发病和进展中的作用。我们研究的独特之处 包括对母乳进行蛋白质组学分析，以评估BC风险。蛋白质组翻译 从局部微环境（乳房）到全身环境（血液）的签名将允许其 用于检测非哺乳期妇女的BC。我们的提议可能会影响一些医疗和研究 领域：1）预防BC（初级预防），2）确定是什么使乳腺癌易感 发展，和3）确定促进BC生长的生化途径，导致预防性 治疗。该地区赠款还将培训大量的本科生，并指导他们 在生物医学领域的职业生涯。 PHS 398/2590（Rev.06/09）