Radial Profile Analysis of Epithelial Polarity in Breast Acini: A Tool for Primary (Breast) Cancer Prevention
Radial Profile Analysis of Epithelial Polarity in Breast Acini: A Tool for Primary (Breast) Cancer Prevention
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DOI：
10.3389/fmed.2019.00314
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发表时间：
2020-01-10
影响因子：
3.9
通讯作者：
Vidi, Pierre-Alexandre
中科院分区：
文献类型：
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作者：
Manning, Lawton;Holmes, Julia;Vidi, Pierre-Alexandre
就患者的生活质量和医疗费用而言，预防癌症远远优于治疗疾病。然而，为了筛选化学预防药物或评估旨在降低癌症风险的干预措施，需要定量的风险读数。在乳腺和其他上皮起源的器官中，顶-底极性是体内平衡的关键，也是癌症发生过程中最先丧失的组织特征之一。因此，顶-底极性可被用作癌症风险的“结构”决定因素。量化上皮极性标志物定位的经典方法是由训练有素的研究人员在显微镜下进行视觉评分。这种方法是时间密集型的，并且限于低吞吐量。为了提高速度，准确性和评分量，我们开发了一种算法，基本上取代了人眼，客观地量化乳腺腺泡（腺泡）显微镜图像中的上皮极性。根据核染色鉴定培养物中的腺泡，并将相应的面具分成等宽的同心梯田。该位置信息用于计算极性标记的径向强度分布（RP）。具有陡峭斜率的剖面代表极化结构，而更多的水平曲线指示非极化腺泡。为了比较治疗效果，将RP曲线整合到极性的汇总值中。我们设想将这种方法应用于腺泡类器官的初级癌症预防研究，特别是（1）筛选化学预防药物，（2）对可疑致癌物和药理学命中化合物进行毒理学评估，以及（3）对癌症风险和降低风险的干预措施进行个性化评估。为MATLAB计算环境和没有信息学知识的用户开发的RadialProfiler算法在开放科学框架（OSF）上公开提供。
Preventing cancer is vastly better than treating the disease in terms of a patient's quality of life and healthcare costs. Yet, to screen for chemopreventative drugs or evaluate interventions aimed at lowering cancer risk, quantitative readouts of risk are needed. In the breast and in other organs of epithelial origin, apical-basal polarity is key to homeostasis and is one of the first tissue characteristics lost during cancer initiation. Therefore, apical-basal polarity may be leveraged as an "architectural" determinant of cancer risk. A classic approach to quantify the localization of epithelial polarity markers is visual scoring at the microscope by trained investigators. This approach is time-intensive and limited to low throughput. To increase the speed, accuracy, and scoring volume, we developed an algorithm that essentially replaces the human eye to objectively quantify epithelial polarity in microscopy images of breast glandular units (acini). Acini in culture are identified based on a nuclear stain and the corresponding masks are divided into concentric terraces of equal width. This positional information is used to calculate radial intensity profiles (RP) of polarity markers. Profiles with a steep slope represent polarized structures, whereas more horizontal curves are indicative of non-polarized acini. To compare treatment effects, RP curves are integrated into summary values of polarity. We envision applications of this method for primary cancer prevention research with acini organoids, specifically (1) to screen for chemoprevention drugs, (2) for toxicological assessment of suspected carcinogens and pharmacological hit compounds, and (3) for personalized evaluation of cancer risk and risk-reducing interventions. The RadialProfiler algorithm developed for the MATLAB computing environment and for users without prior informatics knowledge is publicly available on the Open Science Framework (OSF).