Evaluation of plasma microRNA-122, high-mobility group box 1 and keratin-18 concentrations to stratify acute gallstone disease: a pilot observational cohort study in an emergency general surgery unit

Abstract

ObjectiveTo obtain pilot data to evaluate the discriminatory power of biomarkers microRNA-122 (miR-122), high-mobility group box 1 (HMGB1), full-length keratin-18 (flk-18) and caspase-cleaved keratin-18 (cck-18) in plasma to identify potential biliary complications that may require acute intervention.DesignAn observational biomarker cohort pilot study.SettingIn a Scottish University teaching hospital for 12 months beginning on 3 September 2014.ParticipantsBlood samples were collected from adults (≥16 years old) referred with acute biliary-type symptoms who have presented to hospital within 24 hours prior were recruited. Patients unable or refused to give informed consent or were transferred from a hospital outside the National Health Service regional trust were excluded.Primary outcome measuresTo evaluate whether circulating miR-122, HMGB1, flk-18 and cck-18 can discriminate between people with and without gallstone disease and uncomplicated from complicated gallstone disease during the first 24 hours of hospital admission.Results300 patients were screened of which 285 patients were included. Plasma miR-122, cck-18 and flk-18 concentrations were increased in patients with gallstones compared with those without (miR-122: median: 2.89×104 copies/mL vs 0.90×104 copies/mL (p<0.001); cck-18: 121.2 U/L vs 103.5 U/L (p=0.031); flk-18: 252.4 U/L vs 145.1 U/L (p<0.001)). Uncomplicated gallstone disease was associated with higher miR-122 and cck-18 concentrations than complicated disease (miR-122: 5.72×104 copies/mL vs 2.26×104 copies/mL (p=0.023); cck-18: 139.7 U/L vs 113.6 U/L (p=0.047)). There was no significant difference in HMGB1 concentration between patients with and without gallstones (p=0.559). Separation between groups for all biomarkers was modest.ConclusionmiR-122 and keratin-18 plasma concentrations are elevated in patients with gallstones. However, this result is confounded by the association between biomarker concentrations, age and gender. In this pilot study, miR-122 and keratin-18 were not sufficiently discriminatory to be progressed as clinically useful biomarkers in this context.

Effects of the timing of laparoscopic cholecystectomy after endoscopic retrograde cholangiopancreatography on liver, bile, and inflammatory indices and cholecysto-choledocholithiasis patient prognoses

“…Cholecysto-choledocholithiasis may cause complications such as acute or chronic angiocholitis, obstructive jaundice, biliary pancreatitis, and liver function injury, or could be even fatal (5). Therefore, patients diagnosed with cholecystocholedocholithiasis should receive treatment immediately.…”

The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone

“…Joshi et al investigated 4 novel susceptibility loci ( SULT2A1 , TM4SF4 , GCKR , and CYP7A1 ) and confirmed one known locus ( ABCG8 ) of CG ( Joshi et al, 2016 ). Th’ng et al (2018) reported that plasma miR-122, ull-length keratin-18 (flk-18) and caspase-cleaved keratin-18 (cck-18) concentrations were increased in patients with gallstones compared with those without. In the present study, after the mouse model of CG was successfully constructed, 181 DE-mRNAs (including 104 up-regulated mRNAs and 77 down-regulated mRNAs) and 33 DE-lncRNAs (including 17 up-regulated lncRNAs and 16 down-regulated lncRNAs) between model and normal groups were screened.…”