Liver FoxO1 overexpression is positively associated with the degree of liver injury in cirrhotic patients
Author:
Fernández-Galán Esther1ORCID, Sandalinas Silvia1, Macias-Muñoz Laura1ORCID, Portolés Irene2, Ribera Jordi2, Morales-Romero Blai1, Pauta Montse2, Casals Gregori123, Boix Loreto24, Jiménez Wladimiro125, Morales-Ruiz Manuel1235ORCID
Affiliation:
1. Biochemistry and Molecular Genetics Department-CDB , Hospital Clínic of Barcelona , Barcelona , Spain 2. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) , Barcelona , Spain 3. Commission for the Biochemical Assessment of Hepatic Disease-SEQCML , Barcelona , Spain 4. Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic of Barcelona , Barcelona , Spain 5. Department of Biomedicine-Biochemistry Unit , Faculty of Medicine and Health Sciences, University of Barcelona , Barcelona , Spain
Abstract
Abstract
Objectives
Chronic liver disease and related complications, cirrhosis and hepatocellular carcinoma, are associated with high mortality. Curative treatments, partial hepatectomy or liver transplantation, have limited applicability in patients with cirrhosis due to the poor liver regenerative capacity. Thus, we need to find new diagnostic and therapeutic alternatives, to block the disease progression and to improve the survival of patients. In this context, preclinical studies have demonstrated the key role of the protein kinase B (Akt) in liver dysfunction, but the status of Akt and its targets in patients with chronic hepatopathy remains unknown. Aims: To determine the activation status of the Akt pathway and their association with liver functionality in cirrhotic patients.
Methods
This retrospective study includes liver tissue samples from 36 hepatectomized patients with (n=27) and without (n=9) cirrhosis. Multiplex analysis of proteins involved in the Akt/mTOR pathway was performed using a Luminex panel and Western blot. Conventional liver function tests were determined in serum before resection surgery.
Results
Akt and forkhead box protein O1 (FoxO1) are overexpressed in the liver of cirrhotic patients: (2.1 vs. 1.0 densitometric relative units (DRU); p<0.01, and 9.5 vs. 4.4 DRU; p<0.01, respectively). FoxO1 showed the best correlation with markers of liver injury (aspartate aminotransferase (ASAT): r=0.51, p<0.05; alanine aminotransferase (ALAT): r=0.49, p<0.05), and was the only enzyme in the Akt pathway identified as an independent predictor of ASAT and ALAT levels.
Conclusions
The intrahepatic expression of FoxO1 could have clinical utility as a potential prognostic marker for patients with advanced liver disease.
Funder
Instituto de Salud Carlos III Agència de Gestió d’Ajuts Universitaris i de Recerca Agencia Estatal de Investigación
Publisher
Walter de Gruyter GmbH
Subject
Medical Laboratory Technology,Education,Medicine (miscellaneous)
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