Analysis of the expression level of genes associated with the metabolism of exogenous substances and DNA reparation in patients suffering from bladder cancer

Abstract

IntroductionBladder cancer is a result of the interaction between urine metabolites that come into contact with the bladder mucosa and a certain hereditary predisposition. AimThe aim of the study is to determine the expression level of genes, involved in the metabolism of xenobiotics that are metabolized to substances with carcinogenic potential, as well as the expression levels of genes involved in DNA reparation.Materials and Methods A total of 16 samples from transitional cell bladder cancer were analyzed - four stage pTa, four pT1, five pT2 and three control samples. Expression analysis was done via PAHS-004 Human Cancer Drug Resistance & Metabolism PCR Array on 29 genes, known to take part in DNA reparation and biotransformation of the xenobiotics: APC, ATM, BRCA1, BRCA2, ERCC3, MSH2, XPA, XPC, ARNT, BLMH, CLPTM1L, CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, DHFR, EPHX1, GSK3A, GSTP1, NAT2, SOD1, SULT1E1 (STE) and TPMT. Increased/decreased expression levels were defined by a fivefold change.Results None of the reparative genes showed increased expression. XPA and APC had a decreased expression, ranging from 6 to 30 times, in the highest number of samples: 11 of 13 for XPA and 10 of 13 for APC.Genes related to metabolism of xenobiotics also showed normal or decreased expression. Only three samples from pTa stage showed up-regulation of the CYP3A5 gene, ranging from 6 to 11 times. The rest of the samples showed normal expressions. Only one sample - low differentiated T2 bladder tumor, grade II, stage G3 showed an increased expression of the genes CLPTM1L, CYP1A1 and GSTP1