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

项目总结 乳腺癌是世界上女性最常见的癌症。乳腺癌在早期发现时 在晚期，它可以被有效地治疗甚至治愈，但在后期治疗病人是非常困难的。因此， 乳腺癌的早期发现至关重要。乳房X光检查是目前乳腺癌的黄金标准。 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名妇女中只有不到5人实际患有这种疾病。因此，大多数 异常乳房X光检查是假阳性，需要进一步检查，包括昂贵的乳房 成像和活组织检查，这可能会导致心理痛苦。据美国癌症协会称 (美国癌症协会)，大约10%的做过乳房X光检查的女性会被召回进行更多的检查，但只有8%到10% 其中，女性需要做活组织检查，80%的活组织检查结果是良性的。因此，广大的 大多数女性都会接受不必要的调查。 我们的目标是识别循环中的脂质和miRNA签名，这些签名可以可靠地作为伴侣使用 诊断工具与筛查乳房X光检查相结合，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，我们已经确定了一个由15个血浆组成的小组 能够区分早期癌症和良性病变的脂质种类，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对区分的血浆miRNA比率 从良性样本中提取乳腺癌的准确率超过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，以提高对 对于乳腺癌的早期发现，我们提出了以下目标：1.验证和检验乳腺癌的预测价值 循环血脂标记物用于乳腺癌的早期检测。2.建立循环中的miRNA标记 用于乳腺癌的早期检测。3.早期整合循环脂质和miRNA标志物 乳腺癌的检测。

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.