Author/Authors :
Montazeri, Vahideh Department of Toxicology and Pharmacology - Faculty of Pharmacy - Tehran University of Medical Sciences, Tehran, Iran , Ghahremani, Mohammad Hossein Department of Toxicology and Pharmacology - Faculty of Pharmacy - Tehran University of Medical Sciences, Tehran, Iran , Montazeri, Hamed Department of Pharmaceutical Biotechnology - School of Pharmacy - International Campus, Iran University of Medical Sciences, Tehran, Iran , Hasanzad, Mandana Medical Genomics Research Center - Tehran Medical Sciences - Islamic Azad University, Tehran, Iran , Safavi, Majid Urology Research Center - Tehran University of Medical Sciences, Tehran, Iran , Ayati, Mohsan Uro-Oncology Research Center - Tehran University of Medical Sciences, Tehran, Iran , Chehrazi, Mohammad Department of Biostatistics and Epidemiology - School of Public Health - Babol University of Medical Sciences, Babol, Iran , Moghaddam, Baharak Arefi Imam Khomeini Hospital - Tehran University of Medical Sciences, Tehran, Iran , Nasser Ostad, Seyed Department of Toxicology and Pharmacology - Faculty of Pharmacy - Tehran University of Medical Sciences, Tehran, Iran
Abstract :
One of the main genotoxic drugs used in bladder cancer chemotherapy is cisplatin. While it is applied in most types of cancers, resistance to cisplatin is wildly common. In order to overcome drug resistance, it is necessary to determine a predictive marker. This study was conducted to provide basic data for selecting and designing a gene profile for further cohort and RCT studies in the future to improve response to treatment in bladder cancer. The expression levels of ERCC1, MLH1, MSH2, and CTR1 mRNA were determined in the tumor tissue using real-time q-PCR. Progression-free survival (PFS) was analyzed in term of the level of genes expression. The results revealed that the level of ERCC1 mRNA expression was higher in the recurrence (R) group compared to the no recurrence (NR) group. Moreover, the PFS time was increased in the patients with an ERCC1 expression level of below 1.57. The level of MLH1 and MSH2 mRNA expression was lower in the R group compared to the NR group; therefore, PFS time was increased in the patients with MLH1 and MSH2 gene expression levels above the cutoff point. While the level of CTR1 mRNA expression was higher in the R group versus the NR group, the PFS time was longer in the patients with CTR1 expression levels of below 1.265 compared to the patients with high levels of CTR1 expression. It can be concluded that the level of ERCC1, MLH1, MSH2, and CTR1 mRNA expression may be associated with PFS time as possible therapeutic targets for decreasing cisplatin resistance
Keywords :
Cisplatin , Carcinoma , Transitional cell , Progression-free survival , Copper transporter 1 protein , Human
