Study on enhancement of hypofractionated radiotherapy sensitivity in non-small cell lung cancer by tumor suppressor gene DKK2
10.3760/cma.j.cn.115807-20221130-00345
- VernacularTitle:抑癌基因DKK2增强非小细胞肺癌大分割放疗敏感性的研究
- Author:
Can WANG
1
;
Yue XIE
;
Dan TAO
;
Yuqing WANG
;
Lin XIE
;
Deqinq LIU
;
Qingchun DIAO
;
Jing LI
Author Information
1. 重庆大学附属肿瘤医院，肿瘤转移与个体化诊治转化研究重庆市重点实验室，重庆 400030
- Keywords:
Non-small cell lung cancer;
DKK2;
Hypofractionated radiotherapy
- From:
Chinese Journal of Endocrine Surgery
2023;17(5):613-618
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the expression, methylation and prognosis of DKK2 in non-small cell lung cancer, and also its effect and correlation with the sensitivity of hypofractionated radiotherapy sensitivity in non-small cell lung cancer.Methods:qPCR, online database and Kaplan-Meier survival curve were used to detect the expression, methylation and prognosis of DKK2 in NSCLC samples. A549 cells was set as the research objects, and cloning formation experiment and Western blot were used to evaluated the effects of DKK2 on hypofractionated radiotherapy in NSCLC.Results:Compared with the normal tissues, the expression of DKK2 mRNA in NSCLC samples was down-regulaged [ (0.00042±0.0001) vs (0.00065±0.0002), P<0.001]. Data taken from an online methylation database showed that compared with normal tissue, DKK2 hypermethylated in NSCLC, and its methylation was significantly negatively correlated with the mRNA expression. Downregulated DKK2 expression was inversely correlated with its methylation status ( P=0.034). The hypofractionated radiotherapy sensitivity of NSCLC patients was 53.3%. Compared with radiosensitivity group, DKK2 mRNA expression was significantly down-regulated in radioresistance group[ (0.00064±0.0002) vs (0.00043±0.0002), P<0.001]. The progression free survival of radiotherapy sensitive group was better than that of radiotherapy resistant group (median PFS: 21.4 months vs 4.6 months). Ectopic expression of DKK2 in A549 lines inhibited colony formation after irradiation with 4 Gy X-ray radiotherapy. Western blot further showed that restoration of DKK2 expression resulted in upregulation of DNA damage markers γ-H2AX[ (1.00±0.24) vs (3.22±0.41), P<0.001], and the difference was statistically significant. Conclusion:DKK2 expression is downregulated in NSCLC due to methylation, which may be acted as an important target to predict the hypofractionated radiotherapy sensitivity of NSCLC.
