The Relationship Between Expression Of TopoisomeraseⅡα And Efficacy Of Anthraclines In Patients With Bladder Cancer

Objective Urothelial carcinoma of the bladder(BC) is the ninth most common malignancy worldwide. For the past few decades, adjuvant intravesical treatment with anthracyclines have been performed as the first-line therapy for patients with nonmuscle invasive bladder cancer(NMIBC) after initial transurethral resection of bladder tumor(TURBT). However, predicting patients who are destined to fail anthracyclines treatment is still a very difficult task and need further discussion. Anthracyclines, one of cell cycle non-specific drugs, play a major role on the DNA topoisomerase and inhibit DNA repair function to suppress tumor growth. TopoisomeraseⅡα(topoisomeraseⅡα, TopoⅡα) is the targets of the anthracyclines drugs and located in chromosome 17 q12-21. DNA replication requires topoisomerase to relax the double-strands and anthracyclines drugs can act on TopoⅡα to suppress tumor growth.In this study, we detected the expression levels of TopoⅡα mRNA in NMIBC by the branch DNA-chip technology and assessed the association between TopoⅡα m RNA levels and the efficacy of anthracyclines.Materials and Methods From January 2012 through October 2014, a total of 40 consecutive patients with NMIBC undergoing TUR-BT at the Second Hospital of Tianjin Medical University were included in this study. Of patients 29 were males and 11 females; the mean age was 60.15 ± 12.39(range 31 to 86) years. Tumors were staged and graded according to standard criteria. Twenty-one case were defined as low-grade papillary urothelial carcinoma and 19 cases were high-grade papillary urothelial carcinoma. In this study, all of 40 cases received one cycle of intravesical treatment(anthracyclines) and the following up have been made for 12 months after surgery.Statistical analysis was performed using SPSS 19.0 software. we used the Chisquare(χ2) test to compare the expression levels of TopoⅡα m RNA and the efficacy of anthracyclines. The tests were two-sided and a P value ≤0.05 was considered to indicate statistical significance.Results 1. Expression levels of TopoⅡα m RNA of bladder carcinomaOf the 40 patients, 9(22.5%) had high levels of expression levels of TopoⅡα m RNA, 19(47.5%) cases are medium levels and 12(30%) participants are low levels.2. The clinical-pathology features of bladder cancer and the expression levels of TopoⅡα m RNAThere was no significant correlation between the expression levels of TopoⅡα and patients’ age, gender, tumor size, multifocality or other parameters. However, the m RNA expression levels of TopoⅡα was significant associated with high-grade tumors than in patients with low-grade tumors(15 cases,37.5% and 2 cases,5%, respectively; P <0.05).3. The efficacy of intravesical anthracycline and the expression levels of TopoⅡα m RNAThe expression levels of TopoⅡα m RNA exhibited a strong positive correlation with the efficacy of intravesical anthracycline(P <0.05).Conclusions1. The TopoⅡα mRNA can be detected in bladder cancer and the expression levels of TopoⅡα mRNA were different.2. There is no significant correlation between the expression levels of TopoⅡα m RNA and patients’ age, gender, tumor size, multifocality or other factors, while its expression levels was positive correlated with high grade patients.3. There was significant correlation between the efficacy of intravesical anthracycline and the expression levels of TopoⅡα m RNA. TopoⅡα is a potential target of anthracyclines drugs and can affect the sensitivity of chemotherapy, thus could be used as an important predictor of clinical outcomes.