Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Int J Mol Sci. 2019 Jul 25;20(15):3635. doi: 10.3390/ijms20153635.
In the era of precision medicine, radiotherapy strategies should be determined based on genetic profiles that predict tumor radiosensitivity. Accordingly, pre-clinical research aimed at discovering clinically applicable genetic profiles is needed. However, how a given genetic profile affects cancer cell radiosensitivity is unclear. To address this issue, we performed a pilot in vitro study by utilizing mutational status as a model for genetic profile. Clonogenic assays of mutant ( = 6) and wild-type ( = 9) non-small cell lung carcinoma (NSCLC) cell lines were performed independently by two oncologists. Clonogenic survival parameters SF, SF, SF, SF, mean inactivation dose (MID), D, D, α, and β were obtained using the linear quadratic model. The differences in the clonogenic survival parameters between the mutant and wild-type cell lines were assessed using the Mann-Whitney U test. As a result, for both datasets, the values for SF, SF, D, α, and α/β were below 0.05, and those for SF were lowest. These data indicate that a genetic profile of NSCLC cell lines might be predictive for their radiation response; i.e., mutant cell lines might be more sensitive to low dose- and low fraction sized-irradiation.
在精准医学时代，放疗策略应基于预测肿瘤放射敏感性的基因谱来确定。因此，需要开展临床前研究以发现具有临床应用价值的基因谱。然而，特定的基因谱如何影响癌细胞的放射敏感性尚不清楚。为了解决这个问题，我们进行了一项体外初步研究，利用突变状态作为基因谱的模型。由两位肿瘤学家分别独立对突变型（n=6）和野生型（n=9）非小细胞肺癌（NSCLC）细胞系进行集落形成试验。采用线性二次模型获得集落形成存活参数 SF、SF、SF、SF、平均失活剂量（MID）、D、D、α 和β。使用曼-惠特尼 U 检验评估突变型和野生型细胞系之间集落形成存活参数的差异。结果，对于两个数据集，SF、SF、D、α 和 α/β 的 SF 值均低于 0.05，而 SF 的 SF 值最低。这些数据表明 NSCLC 细胞系的基因谱可能对其辐射反应具有预测性；即突变型细胞系可能对低剂量和小分割照射更敏感。
