Circulating lipid and miRNA markers for early detection of breast cancer among women with abnormal mammograms

循环脂质和 miRNA 标记物用于乳房 X 光检查异常女性乳腺癌的早期检测

• 批准号: 9982252
• 负责人: Youping Deng
• 金额: $ 58.96万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982252
• 关键词: American Cancer Society; Anxiety; Back; Base Ratios; Benign; Biological Markers; Biological Process; Biopsy; Blood; Breast; Breast Cancer Detection; Breast Cancer Early Detection; Breast Cancer Patient; Breast biopsy; Clinical; Clinical Trials; Cooperative Human Tissue Network; Country; Data; Diagnosis; Diagnostic tests; Disease; Early Diagnosis; Gold; Hawaii; Human; Individual; Investigation; Lesion; Lipids; Malignant Neoplasms; Mammographic screening; Mammography; Membrane; Methods; MicroRNAs; Monitor; Pathologic; Patients; Phenotype; Physiological; Plasma; Predictive Value of Tests; Public Health; Publishing; Reverse Transcription; Sampling; Series; Signal Transduction; Technology; Testing; Time; Training; Validation; Woman; Work; base; breast cancer diagnosis; breast imaging; cancer biomarkers; circulating microRNA; classification algorithm; cohort; companion diagnostics; cost; cost effective; diagnostic biomarker; disease diagnosis; early detection biomarkers; follow-up; malignant breast neoplasm; miRNA expression profiling; microRNA biomarkers; mortality; novel; novel marker; patient response; potential biomarker; psychological distress; tool

PROJECT SUMMARY Breast cancer is the most common cancer among women in the world. When breast cancer is found in early stages, it can be effectively treated or even cured, but treating a patient in later stages is very difficult. Thus, early detection of breast cancer is critical. Mammography is the current gold standard for breast cancer screening; however, most women with abnormal mammograms are eventually found not to have breast cancer. Fewer than 5 per 1,000 women actually have the disease when they are screened. Therefore, most abnormal mammograms are false positives that require further investigations including expensive breast imaging and biopsies, which can cause psychological distress. According to the American Cancer Society (ACS), about 10% of women who have a mammogram will be called back for more tests, but only 8% to 10% of those women will need a biopsy and 80% of those biopsies turn out to be benign. Therefore, the vast majority of the women would have undergone unnecessary investigations. Our aim is to identify circulating lipid and miRNA signatures that can be used reliably as a companion diagnostic tool together with screening mammography to reduce the number of unnecessary follow-up investigations, especially invasive biopsy. In our preliminary studies, we have identified a panel of 15 plasma lipid species that were able to distinguish early stage of cancer from benign lesions with over 90% accuracy. Using a ratio based normalization method, we have also found 5 paired plasma miRNA ratios that differentiate breast cancer from benign samples with over 90% accuracy. In order to validate our existing markers and identify potential novel markers, as well as integrate lipid and miRNA markers to increase the accuracy for early detection of breast cancer, we propose the following aims: 1. Validate and test the predictive value of circulating lipid markers for early detection of breast cancer. 2. Establish circulating miRNA markers for early detection of breast cancer. 3. Integrate circulating lipid and miRNA markers for early detection of breast cancer.

项目摘要 乳腺癌是世界女性中最常见的癌症。早期发现乳腺癌 阶段，可以有效地治疗甚至治愈，但是在后期治疗患者非常困难。因此， 乳腺癌的早期发现至关重要。乳腺X线摄影是目前乳腺癌的黄金标准 筛选；但是，大多数患有异常乳房X线照片的女性最终都没有乳房 癌症。筛查时，实际上只有不到每千名妇女患有这种疾病。因此，大多数 乳房X线照片异常是假阳性，需要进一步研究，包括昂贵的乳房 成像和活检，可能导致心理困扰。根据美国癌症协会 （ACS），大约10％的具有乳房X线照片的女性将被召回更多测试，但只有8％至10％ 这些妇女中，需要活检，其中80％的活检结果是良性的。因此，大量 大多数妇女将经历不必要的调查。 我们的目的是确定可靠用作同伴的循环脂质和miRNA签名 诊断工具以及筛查乳房X线摄影以减少不必要的随访数量 调查，尤其是侵入性活检。在我们的初步研究中，我们确定了一个15个等离子体的面板 能够将癌症早期阶段与精度超过90％的良性病变区分开的脂质物种。 使用基于比率的归一化方法，我们还发现了5个分化的配对等离子体miRNA比率 良性样品的乳腺癌精度超过90％。为了验证我们现有的标记和 确定潜在的新颖标记，并整合脂质和miRNA标记，以提高 乳腺癌的早期发现，我们提出以下目的：1。验证和测试的预测值 循环脂质标记物用于早期检测乳腺癌。 2。建立循环miRNA标记 用于早期检测乳腺癌。 3。早期整合循环脂质和miRNA标记 检测乳腺癌。