Collagen structural changes as an early biomarker for breast carcinoma

 描述（由申请人提供）：我们提出胶原蛋白特征，如排列、纤维平直度和宽度，以及细胞外基质组成的其他特征可以用作乳腺癌的早期生物标志物。本提案的目标是确定表征正常、良性和早期疾病的胶原蛋白结构特征的范围，确定这些特征与乳腺摄影密度的关系，并确定最能预测风险、复发和进展的特征。该提案利用了一个多元化的合作团队，其中包括成像和理解肿瘤微环境，乳腺手术，人口健康和生物统计学专家，以及ECM蛋白质组学分析专家。该团队将分析一组患者队列，以开发胶原结构和ECM成分的成像和分析，作为乳腺癌的潜在早期生物标志物。目的：1）表征定义正常状态异质性的胶原蛋白特征。2)表征乳腺癌前和早期病变中的胶原蛋白特征。3)表征代表良性、高危和浸润性乳腺癌的活检组织的蛋白质组学。重要性：该项目符合RFA的目标，即开发和验证联合成像和生物标志物方法，以改善早期癌症检测和早期癌症诊断。我们的发现有可能减少过度诊断和假阳性，并区分致命性和非致命性疾病。

 DESCRIPTION (provided by applicant): We propose that collagen features, such as alignment, fiber straightness and width, and other features of extracellular matrix composition can be used as an early biomarker of breast cancer. It is the goal of this proposal to determine the range of collagen structural features that characterize normal, benign and early disease, to determine how these features relate to mammographic density, and to identify the features that best predict risk, recurrence, and progression. This proposal leverages a diverse collaborative team that includes experts in imaging and understanding the tumor microenvironment, breast surgery, experts in population health and biostatistics, and an expert in proteomic analysis of the ECM. This team will analyze a set of patient cohorts to develop imaging and analysis of collagen structure and ECM composition as a potential early biomarker for breast cancer. Aims: 1) Characterize collagen features that define heterogeneity of the normal state. 2) Characterize collagen features in pre- and early breast cancer lesions. 3) Characterize the proteomics of biopsies representing benign, at risk, and invasive breast cancer. Significance: This project meets the goals of the RFA to develop and validate combined imaging and biomarker approaches to improve early cancer detection and the diagnosis of early-stage cancers. Our findings have the potential to reduce overdiagnosis and false positives and discern lethal from non-lethal disease.