Biomarker evaluation of plasma microRNA-122, high-mobility group box-1 and keratin-18 in acute gallstone disease

ABSTRACT Background A biomarker that stratifies patients with complications of gallstone disease from the denominator pool of people with acute biliary-type symptoms is needed. Circulating microRNA-122 (miRNA-122), high-mobility group box1 (HMGB1), full-length keratin-18 (flk-18) and caspase-cleaved keratin-18 (cck-18) are established hepatocyte injury biomarkers. The aim of this study was to evaluate the discriminatory power of these biomarkers in plasma to identify potential biliary complications that may require acute intervention. Method An observational biomarker cohort study was carried out in a University teaching hospital for 12 months beginning 3 rd September 2014. Blood samples were collected from adults referred with acute biliary-type symptoms. miRNA-122 was measured by quantitative real-time polymerase chain reaction, and HMGB1, cck-18 and flk-18 by ELISA. Results 300 patients were screened and 289 patients were included. Plasma miRNA-122, cck-18 and flk-18 concentrations were increased in patients with gallstones compared to those without ( miRNA-122 : median: 2.89 × 10 4 copies/ml vs. 0.95 × 10 4 copies/ml [P<0.001]; cck-18: 121.9 U/L vs. 104.6 U/L [P = 0.041]; flk-18 : 252.4 U/L vs. 151.8 U/L [P<0.001]). Uncomplicated gallstone disease was associated with higher miRNA-122 and cck-18 concentrations than complicated disease ( miRNA-122 : 5.72 × 10 4 copies/ml vs. 2.26x10 4 copies/ml [P=0.022]; cck-18 : 139.7 U/L vs. 111.4 U/L [P=0.049]). There was no significant difference in HMGB1 concentration between patients with and without gallstones [P=0.480]. Separation between groups for all biomarkers was modest. Conclusion microRNA-122 and keratin-18 plasma concentrations are elevated in patients with gallstones. However, these biomarkers were not sufficiently discriminatory to be progressed as clinically useful biomarkers in this context.