Wechat

Website

Chinese Journal of Oncology Prevention and Treatment ›› 2014, Vol. 6 ›› Issue (2): 114-120.doi: 10.3969/j.issn.1674-5671.2014.02.04

Previous Articles     Next Articles

Dynamics of DNA-dependent protein kinase expression in the development of platinum resistance and correlation with clinical factors

  

  • Online:2014-06-25 Published:2014-07-08

Abstract: Objective To analyze the dynamics of DNA-dependent protein kinase(DNA-PKcs) expression in a nude mouse model of platinum resistance,as well as correlate the dynamics with clinicopathological characteristics of ovarian cancer patients,in order to develop an experimental system for individualized chemotherapy. Methods DNA-PKcs expression was measured by real-time fluores-cence quantitative reverse transcription-polymerase chain reaction(qRT-PCR).Pearson correlation was used to examine associations between expression levels and clinical factors in patients with ovarian cancer.Kaplan-Meier analysis was used to examine association of DNA-PKcs expression with progression-free survival (PFS) and overall survival (OS).Factors affecting patient survival were iden-tified by Cox regression. Result DNA-PKcs expression was significantly lower in transplanted platinum-resistant tumors than in platinum-sensitive controls(P=0.003).Development of drug resistance was associated with a gradual decrease in DNA-PKcs expression,which remained low during the production of platinum-resistant tumor cells.Pearson analysis showed that DNA-PKcs expression correlated negatively with both patient response to platinum treatment and the level of platinum resistance(P=0.000).Kaplan-Meier analysis showed significantly higher survival rates for patients at an early FIGO stage, patients without residual disease,patients who responded to primary platinum treatment,patients sensitive to platinum, and patients with high DNA-PKcs expression(P<0.05).Cox regression identified two factors affecting survival time in patients with ovarian cancer:response to primary platinum treatment(P=0.047) and platinum resistance (P=0.047).DNA-PKcs expression was significantly higher in patients who responded completely to platinum treatment than in patients with stable or progressive tumors(P=0.000).Similarly,DNA-PKcs expression was significantly higher in platinum-sensitive patients than in platinum-resistant ones(P=0.000). Conclusion The development of platinum resistance may be associated with a reduction in DNA-PKcs expression,suggesting that DNA-PKcs may be a useful biomarker of platinum resistance in ovarian cancer.

Key words: Ovarian neoplasm, Drug resistance, Platinum, DNA-dependent protein kinase