Cancer progression involves biomechanical changes within transformed cells and the surrounding extracellular matrix (ECM). The viscoelastic features of fluidity and elasticity that are based on a novel Kelvin-Voigt fractional derivative (KVFD) model were found capable of discriminating normal, benign and malignant breast biopsy tissues on the cellular scale. The improved specificity of KVFD model parameters derives from greater accuracy of fitting the entire approaching force-indentation measurement curve ([Formula: see text] > 0.99) compared with traditional elastic models ([Formula: see text] < 0.86). Moreover, model parameters can be interpreted in terms of histopathological features. First, statistical comparisons reveal there are significant differences (p < 0.001) in elasticity E0, fluidity [Formula: see text], and viscosity [Formula: see text] among healthy, benign, and malignant groups. Malignant breast tissues show low-value, broad-distributions in E0 and with high fluidity [Formula: see text] as compared with healthy and benign tissues. Second, histograms of E0 and [Formula: see text] provide distinctive features by fitting to Gaussian mixture (GM) models. The histograms of E0 and [Formula: see text] are best fit by two kernels GM for malignant tissues, indicating that the cells are soft but with high fluidity and the ECM is stiff but with low fluidity. However, the data suggest one-kernel GM model for benign tissue and a patched uniform distribution for healthy tissue. Third, using fluidity [Formula: see text] as the test statistic, the area under the receiver operator characteristic curve (AUC) is 0.701 ± 0.012 (p < 0.0001) for control versus malignant and 0.706 ± 0.013 (p < 0.0001) for benign versus malignant group. Variations in tissue fluidity and elasticity offer a concise set of viscoelastic biomarkers that correlate well with histopathological features.

中文翻译：

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基于 Kelvin-Voigt 分数阶导数模型，流动性和弹性形成一组简洁的粘弹性生物标志物，用于乳腺癌诊断。

癌症进展涉及转化细胞和周围细胞外基质 (ECM) 内的生物力学变化。发现基于新型 Kelvin-Voigt 分数阶导数 (KVFD) 模型的流动性和弹性的粘弹性特征能够在细胞尺度上区分正常、良性和恶性乳腺活检组织。与传统的弹性模型（[公式：见正文] < 0.86）相比，KVFD 模型参数的改进的特异性源于拟合整个接近力-压痕测量曲线（[公式：见正文] > 0.99）的更高准确性。此外，模型参数可以根据组织病理学特征进行解释。首先，统计比较显示弹性 E0、流动性 [公式：见正文] 存在显着差异 (p < 0.001)，健康、良性和恶性群体之间的粘度[公式：见正文]。与健康和良性组织相比，恶性乳腺组织在 E0 中显示出低值、广泛分布和高流动性 [公式：见正文]。其次，E0 和[公式：见正文] 的直方图通过拟合高斯混合 (GM) 模型提供了独特的特征。E0和[公式：见正文]的直方图最适合恶性组织的两个内核GM，表明细胞柔软但流动性高，ECM僵硬但流动性低。然而，数据表明良性组织的单核 GM 模型和健康组织的补丁均匀分布。第三，使用流动性[公式：见正文]作为检验统计量，受试者操作特征曲线（AUC）下面积为0.701±0.012（p < 0. 0001) 为控制与恶性和 0.706 ± 0.013 (p < 0.0001) 为良性与恶性组。组织流动性和弹性的变化提供了一组与组织病理学特征密切相关的简明粘弹性生物标志物。