title: Sipa1l1 is an early biomarker of liver fibrosis in CCl4-treated rats.
abstract: At present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats. Firstly, serum samples from 18 CCl4-treated rats were clustered into three different groups according to the severity of hepatic and the serum proteome was characterized by label-free LC-MS/MS. Furthermore, three different pooled serum samples obtained from 16 control Wistar rats were also analyzed. Based on the proteomic data obtained, we performed a multivariate analysis which displayed three main cell signaling pathways altered in fibrosis. In cirrhosis, more biological imbalances were detected as well as multi-organ alterations. In addition, hemopexin and signal-induced proliferation-associated 1 like 1 (SIPA1L1) were selected as potential serum markers of liver fibrogenesis among all the analyzed proteins. The results were validated by ELISA in an independent group of 76 fibrotic/cirrhotic rats and 20 controls which confirmed SIPA1L1 as a potential non-invasive biomarker of liver fibrosis. In particular, SIPA1L1 showed a clear diminution in serum samples from fibrotic/cirrhotic rats and a great accuracy at identifying early fibrotic stages. In conclusion, the proteomic analysis of serum samples from CCl4-treated rats has enabled the identification of SIPA1L1 as a non-invasive marker of early liver fibrosis.
authors.affiliation: Biochemistry and Molecular Genetics Service, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Marfà
authors.affiliation: Biochemistry and Molecular Genetics Service, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain Departament de Biomedicina, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Morales-Ruiz
authors.affiliation: Biochemistry and Molecular Genetics Service, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
authors.forename: Denise
authors.initials: D
authors.lastname: Oró
authors.affiliation: Biochemistry and Molecular Genetics Service, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ribera
authors.affiliation: Biochemistry and Molecular Genetics Service, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain Departament de Biomedicina, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Fernández-Varo
authors.affiliation: Biochemistry and Molecular Genetics Service, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain Departament de Biomedicina, University of Barcelona, 08036 Barcelona, Spain wjimenez@clinic.ub.es.
authors.forename: Wladimiro
authors.initials: W
authors.lastname: Jiménez
keywords: Biomarker; E6TP1; Liver fibrosis; Proteomics; SIPA1L1