Budithi Aparajita, Su Sumeyye, Kirshtein Arkadz, Shahriyari Leili
Department of Mathematics and Statistics, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Department of Mathematics, Tufts University, Medford, MA 02155, USA.
Cancers (Basel). 2021 May 27;13(11):2632. doi: 10.3390/cancers13112632.
Many colon cancer patients show resistance to their treatments. Therefore, it is important to consider unique characteristic of each tumor to find the best treatment options for each patient. In this study, we develop a data driven mathematical model for interaction between the tumor microenvironment and FOLFIRI drug agents in colon cancer. Patients are divided into five distinct clusters based on their estimated immune cell fractions obtained from their primary tumors' gene expression data. We then analyze the effects of drugs on cancer cells and immune cells in each group, and we observe different responses to the FOLFIRI drugs between patients in different immune groups. For instance, patients in cluster 3 with the highest T-reg/T-helper ratio respond better to the FOLFIRI treatment, while patients in cluster 2 with the lowest T-reg/T-helper ratio resist the treatment. Moreover, we use ROC curve to validate the model using the tumor status of the patients at their follow up, and the model predicts well for the earlier follow up days.
许多结肠癌患者对其治疗产生耐药性。因此,考虑每个肿瘤的独特特征以找到适合每个患者的最佳治疗方案非常重要。在本研究中,我们开发了一个数据驱动的数学模型,用于研究结肠癌中肿瘤微环境与FOLFIRI药物制剂之间的相互作用。根据从原发性肿瘤基因表达数据中获得的估计免疫细胞分数,将患者分为五个不同的组群。然后,我们分析药物对每组癌细胞和免疫细胞的影响,并观察不同免疫组患者对FOLFIRI药物的不同反应。例如,T调节细胞/辅助性T细胞比例最高的第3组患者对FOLFIRI治疗反应更好,而T调节细胞/辅助性T细胞比例最低的第2组患者则对该治疗产生耐药性。此外,我们使用ROC曲线,根据患者随访时的肿瘤状态验证该模型,并且该模型对早期随访天数预测良好。