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Archive > Volume 26 Issue 2 > 2019,26(2):213-219. DOI:10.3872/j.issn.1007-385X.2019.02.012 Prev Next
Clinical Research
Correlation between KRAS gene mutation and DTC resistance to 131I radiotherapy and prognosis
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Abstract:
[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.
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Project Supported:
Project supported by Reach of Yunnan Application Fundamental (No.2017FE468)
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