Association of TK1 up-regulation with drug resistance of ovarian cancer

Abstract:

Objective：To analyze the association of thymidine kinase 1（TK1） with drug resistance of ovarian cancer. Methods：GEPI－A online tool was used to detect the mRNA expression of TK1 in normal ovary tissue and ovarian cancer tissue. KM-Plot was used to perform OS survival rate. GEO profiles database was used to analyze the mRNA expression of TK1 in cisplatin sensitive and cisplatin resistant A2780 cell lines. Comprehensive bioinformatic analyses，protein interaction analysis，genetic pathway enrichment analysis，text mining and miRNA-mRNA interaction analysis were performed to further demonstrate TK1 regulated ovarian cancer drug resis－tance and investigate its potential mechanism. Results：The TK1 expression in the cancer tissue was significantly higher than that in the normal tissue. The high TK1 expression was related with patients’ low survival rates. The TK1 expression in cisplatin resistant A2780 was higher when compared with cisplatin sensitive A2780. Most genes that were closely interacted with TK1 were associated with drug resistance of ovarian cancer. By using genetic pathway enrichment to analyze genes interacted with TK1，it was found that most enriched pathways were related with metabolism. Text mining showed that cell cycle，cell proliferation，S phase，endocytosis and phosphorylation were significantly associated with TK1 protein，ovarian cancer and drug resistance. According to the miRNA-mRNA interaction analysis，it was showed that 11 TK1-targeted microRNAs were related to drug resistance of ovarian cancer or other cancers. Conclusion：Up-regulation of TK1 is associated with drug resistance of ovarian cancer.