Mathematical modeling for mutator phenotype and clonal selection advantage in the risk analysis of lung cancer
Mathematical modeling for mutator phenotype and clonal selection advantage in the risk analysis of lung cancer
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DOI：
10.1007/s12064-022-00371-z
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发表时间：
2022-06-04
影响因子：
1.1
通讯作者：
Zhang，Xinan
中科院分区：
文献类型：
--
作者：
Li，Lingling;Zhao，Ting;Zhang，Xinan
癌症是导致人类死亡的主要疾病之一。尽管已经进行了大量的研究工作来调查癌症疾病的发生和发展，但是关于赋予克隆优势的突变的功能和由稳定性基因突变引起的增变子表型的重要性仍然是一个活跃的争论。为了进一步解决这一问题，我们根据美国监测流行病学和最终结果登记处的非小细胞肺癌和小细胞肺癌的发病率数据建立了一个数学模型。通过对关键生物学参数的分析，探讨抑制肺癌风险的潜在有效措施。虽然第一个事件是基因突变导致肺癌细胞的克隆性扩增，但模拟结果表明，癌细胞的克隆性优势本身不足以导致肿瘤发生。我们的分析表明，保持遗传稳定性的基因突变在肺癌的发展中至关重要。这意味着突变子表型是诊断肺癌的重要指标，可以使肺癌的早期发现和治疗，有效地降低肺癌的风险。此外，参数分析表明，通过抑制正常细胞向突变细胞的转化率和具有较少基因突变的细胞的克隆扩增，将高度有效地控制肺癌的风险。
Cancer is one of the leading diseases for human mortality. Although substantial research works have been conducted to investigate the initiation and progression of cancer disease, it is still an active debate regarding the function of mutations conferring a clone advantage and the importance of mutator phenotypes caused by the mutation of stability genes. To address this issue further, we develop a mathematical model based on the incidence data of non-small cell lung cancer and small cell lung cancer from the Surveillance Epidemiology and End Results registry in the USA. The key biological parameters have been analyzed to investigate the potential effective measures for inhibiting the risk of lung cancer. Although the first event is the gene mutation that leads to clonal expansion of cells for lung cancer, the simulation results show that the clonal advantage of cancer cells alone is insufficient to cause tumorigenesis. Our analysis suggests that mutations in genes that keep genetic stability are critical in the development of lung cancer. This implies that mutator phenotype is an important indicator for the diagnosis of lung cancer, which can enable early detection and treatment to reduce the risk of lung cancer effectively. Furthermore, the parameter analysis indicates that it would be highly effective to control the risk of lung cancer by inhibiting the transformation rate from the normal cells to mutated cells and the clonal expansion of cells with fewer gene mutations.