IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
IN SILICO IDENTIFICATION AND IN VIVO VALIDATION OF NON-INVASIVE BIOMARKERS FOR LIVER FIBROSIS
Autor/es:
GIRAUDI PABLO; GAMBARO SABRINA ELIANA; CHACKELEVICIUS CARLA; GIURICIN M.; CROCE LORY; BONAZZA D; SOARDO G.; DE MANZINI N.; TIRIBELLI CLAUDIO; PALMISANO S; ROSSO NATALIA
Lugar:
Bacelona
Reunión:
Congreso; The International Liver Congress? 2016, EASL; 2016
Institución organizadora:
European Association for the Study of the Liver, EASL
Resumen:
Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is aprogressive liver injury, which can lead to non-alcoholicsteatohepatitis and progress towards cirrhosis. It is tightlyassociated with obesity and type 2 diabetes mellitus. Currently, thegold standard for the diagnosis relies on the liver biopsy. Reliablenon-invasive tools are still missing. The aim of this study was toidentify novel biomarkers by in silico studies and validate theirspecificity in serum of a NAFLD cohort.Methods: in silico protein-protein interactions were used to build abiological network among interested genes involved in fibrogenesis(CK18, IBP3, LCP1, LGALS1, LAMB1, HACTA, TIMP-2 and MMP2). Fromthis analysis were identified: CD44, SPARC, EGFR and IGF2, assecreted factors with clinical relevance as candidate biomarkers.Gene expression of interest and candidate genes were assessed bothin liver and blood by qPCR. Plasmatic concentration of candidates wasmeasured by ELISA.45 adult morbid obese consenting patients (BMI > 35 kg/m2; 17males and 28 females, age range: 19?63) undergoing bariatricsurgery were enrolled. Wedge liver biopsy was performed andblood samples were collected. Exclusion criteria were alcoholconsumption, viral hepatitis infection, known chronic liver disease.Biopsy was assessed according to Brunt?s fibrosis Score.Results: Hepatic gene expression analysis showed an increase of thegenes of interest, which correlated with the stage of fibrosis.Interestingly, the expression of candidates genes: IGF2, CD44 andSPARC, also increased with the fibrosis? stage. They allowed todistinguish grade 0 vs. 2 of liver fibrosis (folds of expression: 1.0 ± 0.3vs.12.1 ± 4.0; 1.0 ± 0.5 vs. 4.9 ± 2.2 and 1.0 ± 0.4 vs 11.4 ± 4.4, p < 0.05, p< 0.05 and p < 0.01, respectively). Only CK18 hepatic expressioncorrelated with both steatosis grade and fibrosis stage. Nocorrelations between liver and blood gene expression was observedfor any studied gene. IGF2 plasmatic level was inversely correlatedwith fibrosis score (p < 0.01), whereas EGFR levels increased withfibrosis score (p < 0.01).Conclusions: These preliminary data show that plasma levels of theidentified soluble markers (IGF2 and EGFR) seem to correlate withthe initial stage of fibrosis. This data could contribute to thedevelopment of future non-invasive diagnosis tools.U05SPFRA14 ? FRA 2014 (CdA dd. 19.12.2014) FIF grant. PJG wassponsored by Fondazione Umberto Veronesi (Grants 2015). SEG byProyectonutrizione 297 CTGAS CMC by MAE.