Competence Center Bioinformatics, Institute for Applied Computer Science, University of Applied Sciences Stralsund, Zur Schwedenschanze 15, 18435, Stralsund, Germany.
Institute for Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
BMC Cancer. 2020 Jun 5;20(1):524. doi: 10.1186/s12885-020-07015-9.
Xenograft mouse tumor models are used to study mechanisms of tumor growth and metastasis formation and to investigate the efficacy of different therapeutic interventions. After injection the engrafted cells form a local tumor nodule. Following an initial lag period of several days, the size of the tumor is measured periodically throughout the experiment using calipers. This method of determining tumor size is error prone because the measurement is two-dimensional (calipers do not measure tumor depth). Primary tumor growth can be described mathematically by suitable growth functions, the choice of which is not always obvious. Growth parameters provide information on tumor growth and are determined by applying nonlinear curve fitting.
We used self-generated synthetic data including random measurement errors to research the accuracy of parameter estimation based on caliper measured tumor data. Fit metrics were investigated to identify the most appropriate growth function for a given synthetic dataset. We studied the effects of measuring tumor size at different frequencies on the accuracy and precision of the estimated parameters. For curve fitting with fixed initial tumor volume, we varied this fixed initial volume during the fitting process to investigate the effect on the resulting estimated parameters. We determined the number of surviving engrafted tumor cells after injection using ex vivo bioluminescence imaging, to demonstrate the effect on experiments of incorrect assumptions about the initial tumor volume.
To select a suitable growth function, measurement data from at least 15 animals should be considered. Tumor volume should be measured at least every three days to estimate accurate growth parameters. Daily measurement of the tumor volume is the most accurate way to improve long-term predictability of tumor growth. The initial tumor volume needs to have a fixed value in order to achieve meaningful results. An incorrect value for the initial tumor volume leads to large deviations in the resulting growth parameters.
The actual number of cancer cells engrafting directly after subcutaneous injection is critical for future tumor growth and distinctly influences the parameters for tumor growth determined by curve fitting.
异种移植小鼠肿瘤模型用于研究肿瘤生长和转移形成的机制，并研究不同治疗干预措施的疗效。接种后，移植细胞会在局部形成肿瘤结节。在最初的几天潜伏期后，实验过程中定期使用卡尺测量肿瘤的大小。这种确定肿瘤大小的方法存在误差，因为测量是二维的（卡尺无法测量肿瘤深度）。原发性肿瘤生长可以通过合适的生长函数来数学描述，而选择哪种函数并不总是很明显。生长参数提供了关于肿瘤生长的信息，并通过应用非线性曲线拟合来确定。
我们使用包括随机测量误差在内的自生成合成数据来研究基于卡尺测量的肿瘤数据的参数估计准确性。研究了拟合指标，以确定给定合成数据集最适合的生长函数。我们研究了在不同频率下测量肿瘤大小对估计参数的准确性和精度的影响。对于具有固定初始肿瘤体积的曲线拟合，我们在拟合过程中改变这个固定初始体积，以研究对生成的估计参数的影响。我们使用离体生物发光成像确定注射后存活的移植肿瘤细胞数量，以证明对初始肿瘤体积的不正确假设对实验的影响。
为了选择合适的生长函数，至少应考虑 15 只动物的测量数据。为了估计准确的生长参数，肿瘤体积应至少每三天测量一次。每天测量肿瘤体积是提高肿瘤生长长期预测能力的最准确方法。为了获得有意义的结果，初始肿瘤体积需要具有固定值。初始肿瘤体积的值不正确会导致生成的生长参数产生较大偏差。
皮下注射后直接植入的癌细胞数量对于未来的肿瘤生长至关重要，并明显影响通过曲线拟合确定的肿瘤生长参数。
