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. 2019 Jul 25;20(15):3635.
doi: 10.3390/ijms20153635.

Radiosensitivity Differences between EGFR Mutant and Wild-Type Lung Cancer Cells are Larger at Lower Doses

Mai Anakura  1 , Ankita Nachankar  1 , Daijiro Kobayashi  1 , Napapat Amornwichet  2 , Yuka Hirota  1 , Atsushi Shibata  3 , Takahiro Oike  4 , Takashi Nakano  1
Affiliations

Radiosensitivity Differences between EGFR Mutant and Wild-Type Lung Cancer Cells are Larger at Lower Doses

Mai Anakura et al. Int J Mol Sci. .

Abstract

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 EGFR mutational status as a model for genetic profile. Clonogenic assays of EGFR mutant (n = 6) and wild-type (n = 9) non-small cell lung carcinoma (NSCLC) cell lines were performed independently by two oncologists. Clonogenic survival parameters SF2, SF4, SF6, SF8, mean inactivation dose (MID), D10, D50, α, and β were obtained using the linear quadratic model. The differences in the clonogenic survival parameters between the EGFR mutant and wild-type cell lines were assessed using the Mann-Whitney U test. As a result, for both datasets, the p values for SF2, SF4, D50, α, and α/β were below 0.05, and those for SF2 were lowest. These data indicate that a genetic profile of NSCLC cell lines might be predictive for their radiation response; i.e., EGFR mutant cell lines might be more sensitive to low dose- and low fraction sized-irradiation.

Keywords: clonogenic assays; gene mutations; precision medicine; radiation therapy; radiosensitivity.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Dataset A: Survival curves for EGFR mutant (red) and wild-type (blue) non-small cell lung carcinoma cell lines treated with X-rays.
Figure 2
Figure 2
Dataset B: Survival curves for EGFR mutant (red) and wild-type (blue) non-small cell lung carcinoma cell lines treated with X-rays.
Figure 3
Figure 3
Summary of the p values for datasets A and B. MID, mean inactivation dose. Black lines indicate the mean values.
Figure 4
Figure 4
Exemplary presentation of the analyzed parameters for clonogenic survival. (A) Surviving fractions for the cells irradiated with 2, 4, 6, or 8 Gy (SF2, SF4, SF6, and SF8, respectively) are plotted on a semi-logarithmic-scaled graph (indicated as red dots). The survival data were fitted to the LQ model: S = exp(−(αD + βD2)), where S is the surviving fraction and D is the dose (red line indicates the LQ curve; green and blue line indicates its linear and quadratic component, respectively). D10 and D50 are calculated from the LQ model formula, where DX indicates the dose that decreases the surviving fraction to X%. As an example, α/β (2.1), SF4 (0.32), and D10 (6.0) are shown as orange, light blue, and violet arrow, respectively. (B) The same exemplary survival data were plotted on a linear-scaled graph. MID equals the area under the curve (indicated as light red) [11].
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