Correlation between KRAS genemutationandDTC resistance to 131I radiotherapy and prognosis
10.3872/j.issn.1007-385x.2019.02.012
- VernacularTitle:KRAS基因突变与分化型甲状腺癌131I放疗耐受性及预后的关系
- Author:
FENG Zhiping
1
;
CHEN Fukun
1
;
YANG Chuanzhou
1
;
CHEN Ting
1
;
ZHU Jialun
1
;
LIU Chao
1
;
LV Juan
1
;
LU Jianmei
1
;
DENG Zhiyong
1
Author Information
1. Department of Nuclear Medicine, the Third Affiliated Hospital of Kunming Medical University also known as Cancer Hospital of Yunnan Province
- Publication Type:Journal Article
- Keywords:
differentiated thyroid carcinoma;
131I radiation therapy;
KRAS gene;
mutant;
radiotherapy resistant
- From:
Chinese Journal of Cancer Biotherapy
2019;26(2):213-219
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the correlation between KRAS gene mutation and differentiated thyroid carcinoma (DTC) treatment effect and prognosis, and to explore the mechanism. Methods: Clinical tissue samples from DTC patients undergoing 131I Radiotherapy were collected. Then single strand conformation polymorphism analysis of polymerase chain reaction products (PCRC-SSCP) was used to detect KRAS mutation rate in thyroid cancer patients of different TNM stages; p21 protein expression level was detected by real-time quantitative polymerase chain reaction (qPCR) and western blotting. DTC cells were treated by sub-lethal dose of 131I Radiotherapy, and then CCK-8 assay, transwell assay and flow cytometry (FCM) were used to evaluate the changes of cells viability. Animal models were then constructed for verification. Results: The results showed that KRAS gene mutants were increased in 131I-resistant DTC patients; KRAS gene mutation suppressed p21 protein expression and was associated with clinical stage and poor prognosis. In vivo and in vitro experiments proved that sub-lethal dose of 131I increased KRAS gene mutation rate, suppressed p21 expression level, and caused 131I radiotherapy resistance. Reversely, over-expression of KRAS gene could significantly increase p21 expression, and inhibit tumor proliferation and metastasis. Conclusion: KRAS gene mutations were associated with DTC TNM stages and 131I resistance in DTC patients. Sub-lethal dose of 131I treatment could improve 131I resistance in DTC cells line, inversely, over-expressed KRAS gene could increase the sensitivity to 131I radiotherapy in DTC patients.
- Full text:20190212.pdf
