Urinary Excretion Patterns of Pseudouridine and β-Aminoisobutyric Acid in Patients with Tumours of the Urinary Bladder

Abstract

The preoperative and postoperative values of urinary pseudouridine:creatinine (phi:C) and beta-aminoisobutyric acid:creatinine (beta AIB:C) were estimated, in 192 patients with urothelial tumours of the bladder, 92 of whom had not previously been diagnosed. Urinary phi:C ratio correlated with the grade of tumour cell dysplasia (being highest in dysplasia grade 3), and to a lesser extent with the clinical stage. The treatment had no major influence on the excretion ratios. Decreased ratios, or those within the reference range, were associated with a better prognosis than increased ratios, and if both were increased at the same time the risk for progression of the disease was high. The biological tumour markers pseudouridine and beta-aminoisobutyric acid may be helpful in the diagnosis of tumours in the upper urinary tract, and in the follow-up of patients with tumours of the bladder.

Modified nucleosides: an accurate tumour marker for clinical diagnosis of cancer, early detection and therapy control

“…The following seven were the most significant ones: cytidine, N2,N2-dimethylguanine, PCNR, 2-methylguanosine, 1-methylguanosine, pseudouridine and 1-methyladenosine. These nucleosides have already been reported as useful biochemical 'indicators' in malignant diseases (Lakings et al, 1977;Koshida et al, 1985;Holstege et al, 1986;Oerlemans and Lange, 1986;Sander et al, 1986;Rasmuson et al, 1987;Boos et al, 1988;McEntire et al, 1989;Gehrke and Kuo, 1990;Schöch et al, 1990a, b;Kvist et al, 1993;Nakano et al, 1993;Topp et al, 1993;Rasmuson and Björk, 1995;Martinow et al, 1998;Xu et al, 2000;Dudley et al, 2004;Yang et al, 2004;Zheng et al, 2005). Cytidine and uridine were found to be much more increased than reported in other publications.…”

“…Before the samples could be analysed by HPLC, a treatment is necessary to remove the proteins. Other authors reported on using phenyl boronate affinity column for nucleoside isolations (Koshida et al, 1985;Holstege et al, 1986;Oerlemans and Lange, 1986;Sander et al, 1986;Rasmuson et al, 1987;McEntire et al, 1989;Gehrke and Kuo, 1990;Schöch et al, 1990a;Kvist et al, 1993;Nakano et al, 1993;Topp et al, 1993;Rasmuson and Björk, 1995;Martinow et al, 1998;Xu et al, 2000;Yang et al, 2004) or using the Baker SPE system with aromatic sulphonic acid (Schöch et al, 1990b). These fractionation methods of nucleosides from urine were found to be too complex and time consuming to allow the analyses of large numbers of urine samples.…”

“…Urinary excretion of methylated nucleosides, which results from increased turnover and degradation of RNA, especially from transfer ribonucleic acid (tRNA), has been shown to be excreted in increased amounts in the urine of patients with different types of tumours and AIDS (Nakano et al, 1993;Xu et al, 2000;Yang et al, 2004;Zheng et al, 2005). Elevated levels of modified nucleosides have been found in urine from patients with leukaemia and lymphoma (Rasmuson and Björk, 1995), cancer of the lung (McEntire et al, 1989), oesophagus (Masuda et al, 1993), breast (Rasmuson et al, 1987;Nakano et al, 1993;Sasco et al, 1996;Zheng et al, 2005), renal cell carcinoma (Koshida et al, 1985), ovarian cancer (Oerlemans and Lange, 1986), liver cancer (Yang et al, 2004), tumours of the bladder (Kvist et al, 1993), colon cancer (Holstege et al, 1986) and Hodgkin's disease (Martinow et al, 1998). One possible cause is the higher turnover rate of tRNA in tumour tissues than that in normal counterparts as demonstrated by Borek et al (1977).…”

“…However, when a broad spectrum of modified nucleosides has to be determined, the preferred method is high-performance liquid chromatography (HPLC) (Lakings et al, 1977;Koshida et al, 1985;Oerlemans and Lange, 1986;Sander et al, 1986;Rasmuson et al, 1987;McEntire et al, 1989;Gehrke and Kuo, 1990;Schöch et al, 1990a, b;Kvist et al, 1993;Nakano et al, 1993;Topp et al, 1993;Rasmuson and Björk, 1995;Martinow et al, 1998;Xu et al, 2000;Yang et al, 2004).…”

Analysis of urinary nucleosides as potential cancer markers determined using LC–MS technique

“…This process is not, however, dependent on age among adults [17]. Therefore, according to numerous studies, urinary nucleosides have been proposed as possible cancer markers in colorectal [18][19][20], breast [21][22][23][24][25][26], bladder [27][28][29], lymphoma [30,31], thyroid [32] and cervical cancer [33]. So far, several analytical techniques have been applied for nucleosides' determination, including immunoassay [34], capillary electrophoresis (CE) [35] and high performance liquid chromatography (HPLC) [36].…”