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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

基本信息

批准号：
10673061
负责人：
Youping Deng
金额：
$ 53.04万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
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/10673061
关键词：
American Cancer Society Anxiety Base Ratios Benign Biological Markers Biological Process Biopsy Blood Breast Breast Cancer Detection Breast Cancer Early Detection Breast Cancer Patient Breast biopsy Callback Classification Clinical Clinical Trials Cooperative Human Tissue Network Country Data Diagnosis Diagnostic tests Disease Early Diagnosis Harm Reduction 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 Serum Signal Transduction Technology Testing Time Training Validation Woman Work breast cancer diagnosis breast imaging cancer biomarkers circulating microRNA classification algorithm cohort companion diagnostics cost cost effective diagnostic biomarker diagnostic tool diagnostic value disease diagnosis early detection biomarkers follow-up lipidomics malignant breast neoplasm miRNA expression profiling microRNA biomarkers mortality novel novel marker potential biomarker psychological distress tool treatment response

项目摘要

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.

项目概要乳腺癌是世界上女性最常见的癌症。当乳腺癌早期发现时阶段可以有效治疗甚至治愈，但是后期治疗就非常困难了。因此，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光检查异常的女性最终被发现没有乳房癌症。在接受筛查时，每 1000 名女性中实际患有这种疾病的人数不到 5 人。因此，大多数异常的乳房X光检查属于误报，需要进一步的检查，包括昂贵的乳房检查影像学和活检，这可能会导致心理困扰。据美国癌症协会称 (ACS)，大约 10% 接受乳房 X 光检查的女性会被召回进行更多检查，但只有 8% 到 10% 其中的女性需要进行活检，其中 80% 的活检结果是良性的。因此，广大大多数妇女都会接受不必要的调查。我们的目标是识别可以可靠地用作伴侣的循环脂质和 miRNA 特征诊断工具与筛查乳房X光检查一起减少不必要的随访次数调查，特别是侵入性活检。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%。使用基于比率的归一化方法，我们还发现了 5 配对的血浆 miRNA 比率，可以区分从良性样本中提取乳腺癌，准确率超过 90%。为了验证我们现有的标记和识别潜在的新标记，以及整合脂质和 miRNA 标记以提高准确度为了早期发现乳腺癌，我们提出以下目标： 1. 验证和测试预测值用于早期检测乳腺癌的循环脂质标记物。 2. 建立循环 miRNA 标记用于早期发现乳腺癌。 3. 整合循环脂质和 miRNA 标记物以实现早期诊断乳腺癌的检测。