无扰动肿瘤生长的 Montijano-Bergues-Bory-Gompertz 随机模型的参数估计

Beatriz Bonilla-Capilla, Luis Enrique Bergues Cabrales
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摘要

癌症的随机生长涉及内生和外生的不同噪声源。本研究的目的是针对无扰动肿瘤生长动力学提出随机版的 Montijano-Bergues-Bory-Gompertz 方程。通过分析计算得到了肿瘤固有生长速率和生长减速因子的最大似然估计值及其各自的离散时间近似值。针对各自参数的不同值,对该方程的确定性和随机性进行了不同的模拟。确定了平均扩散系数和生长减速因子的极限条件。根据随机 Montijano-Bergues-Bory-Gompertz 方程的几个参数值,计算了无限远处的肿瘤体积。此外,还根据该方程的几个参数计算了肿瘤内在生长率最大似然估计值的描述性统计。结果表明,实体肿瘤的平均扩散系数和生长减速因子值小于各自的极限值。从生长减速因子最大似然估计值的离散时间近似值与肿瘤固有生长率最大似然估计值的离散时间近似值的对比图中可以看出,无扰动肿瘤生长动力学在无血管阶段和血管阶段之间的过渡。这些结果与文献中的不同发现有关。总之,正如之前对其确定性版本所证明的那样,随机 Montijano-Bergues-Bory-Gompertz 方程可以在实验中用于描述未受扰动的肿瘤生长动力学,以估计该方程的参数及其与未受扰动实体肿瘤的生长、进展和转移过程的联系。
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Parameter estimation in the Montijano-Bergues-Bory-Gompertz stochastic model for unperturbed tumor growth
Different sources of noises endogenous and exogenous to the cancer are involved in its stochastic growth. The aim of this study is to propose the stochastic version of Montijano-Bergues-Bory-Gompertz equation for the unperturbed tumor growth kinetics. The maximum likelihood estimators for the intrinsic tumor growth rate and the growth decelerating factor, and their respective discrete time approximations were analytically calculated. Different simulations of the deterministic and stochastic of this equation were made for different values of their respective parameters. Limit conditions for the average diffusion coefficient and the growth decelerating factor were established. The tumor volume at the infinite was calculated for several values of parameters of the stochastic Montijano-Bergues-Bory-Gompertz equation. Furthermore, descriptive statistic for the maximum likelihood estimators of the intrinsic tumor growth rate was computed for several parameters of this equation. The results evidenced that solid tumors there are for values of the average diffusion coefficient and the growth decelerating factor less than their respective limit values. The transition between avascular and vascular phases of the unperturbed tumor growth kinetics was revealed in the plot of the discrete time approximation for the maximum likelihood estimator of the growth decelerating factor versus the discrete time approximation for the maximum likelihood estimator of the intrinsic tumor growth rate. These results were connected with different findings in the literature. In conclusion, the stochastic Montijano-Bergues-Bory-Gompertz equation may be applied in the experiment to describe the unperturbed tumor growth kinetics, as previously demonstrated for its deterministic version, in order to estimate the parameters of this equation and their connection with processes involved in the growth, progression and metastasis of unperturbed solid tumors.
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