Correlation of adenosine deaminase operating under nitro-oxidative stress with tumor and vascularization in patients with advanced gallbladder carcinoma

Abstract

This study investigates serum redox status and adenosine catabolism markers in relation to tumor and angiogenesis, in patients with gallbladder carcinoma (GBC).The level of adenosine deaminase (ADA) and xanthine oxidase (XO) activities, nitrites (NO 2 -), glutathione (GSH) and malondialdehyde (MDA) were measured in sera of 40 GBC patients and 40 healthy donors. In parallel, 15 tumors at TNM stage IV were scored for CD34 expression and microvessel density (MVD).The results showed that XO and ADA activities, nitrites and MDA levels enhanced by 1.26 (p < 0.01), 2.69, 2.0, and 3.2-fold (p < 0.001), respectively, while those of GSH decreased by 44.6% (p < 0.001). According to receiver operating characteristic (ROC) curve, the optimal cut-off for XO, ADA, MDA, GSH and nitrites were 5.41U/l, 17.02 U/l, 3.72 μM, 36.91 μM and 21.21 μM, respectively. Spearman correlation revealed that ADA activity correlated to nitrites levels (r = 0.3419, p < 0.05) and XO activity (r = 0.5487, p < 0.001). Multivariate binary logistic regression analysis revealed that MDA (OR = 5.78, p < 0.05), ADA (OR = 1.28, p < 0.001) and XO (OR = 2.81, p < 0.05) correlated positively to GBC. CD34 was up expressed in 73.3% of tumors at intermediate to high levels. Multiple regression analysis showed that ADA affected MVD (r = 0.604, p < 0.01).The results suggest that high MDA/GSH ratio is a potential biomarker of GBC. In addition, the oxidative adenosine catabolism indicated that active purine salvage pathway could support tumor progression by sustaining angiogenesis. Highlights:• Adenosine deaminase (ADA), xanthine oxidase (XO) and nitrites increased in GBC; • ADA and XO activities correlated with GBC; • ADA activity supported microvessel density (MVD) in advanced GBC; • High serum MDA/GSH ratio as potential risk factor in GBC.