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: 10218097
• 负责人: Youping Deng
• 金额: $ 56.93万
• 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/10218097
• 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; lipidomics; 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 乳腺癌是世界上妇女最常见的癌症。当乳腺癌被发现在早期 在某些阶段，它可以有效治疗甚至治愈，但治疗晚期患者非常困难。因此，在本发明中， 早期发现乳腺癌至关重要。乳房X光检查是目前乳腺癌的金标准 筛查;然而，大多数乳房X光检查异常的妇女最终发现没有乳房 癌在接受筛查时，每1,000名妇女中只有不到5人实际患有这种疾病。因此多数 异常的乳房X线照片是假阳性，需要进一步的调查，包括昂贵的乳房 成像和活组织检查，这可能会导致心理困扰。根据美国癌症协会 (ACS)，大约10%做过乳房X光检查的女性会被召回做更多的检查，但只有8%到10% 这些妇女将需要活检，80%的活检结果是良性的。因此， 大多数女性都会接受不必要的调查。 我们的目的是确定循环脂质和miRNA的签名，可以可靠地用作伴侣。 诊断工具与筛查性乳房X光检查一起使用，以减少不必要的随访次数 检查，尤其是侵入性活检。在我们的初步研究中，我们已经确定了一组15个血浆 脂质种类能够区分早期癌症和良性病变，准确率超过90%。 使用基于比率的标准化方法，我们还发现了5对血浆miRNA比率， 乳腺癌良性样本的准确率超过90%。为了验证我们现有的标记， 鉴定潜在的新标记物，以及整合脂质和miRNA标记物，以提高 早期发现乳腺癌，我们提出以下目标：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标记物 乳腺癌的早期诊断。3.整合循环脂质和miRNA标记物， 乳腺癌的诊断