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Proteomic profile in the diagnostics of portal hypertension in patients with compensated advanced liver disease

ABSTRACT: Study aim: To compare proteomic profiles of patients with compensated advanced liver disease with and without clinically significant portal hypertension (CSPH) and by analyzing differently expressed proteins to identify potential new serum biomarkers for the early diagnosis of CSPH. Subjects and methods: Patients with compensated advanced liver disease will be included in the study. Two groups will be separated based on the presence of CSPH assessed by hepatic vein pressure gradient. High performance liquid chromatography and mass spectrometry will be used to determine the protein composition of the pooled samples. Bioinformatic tools and literature review will be used to analyze the significance and biologic role of the identified proteins. Expected scientific yield: We expect by analyzing differently expressed proteins and biological processes to identify potential biomarkers of CPSH and to provide additional insight to the pathogenesis of CSPH.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Portal Hypertension

SUBMITTER: Ruđer Novak

LAB HEAD: Lovorka Grgurevic

PROVIDER: PXD040807 | Pride | 2024-02-01

REPOSITORIES: Pride

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Project description:Background/Aim: We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Results: NGS data revealed that exosomal miR-660-5p, miR-125a-5p, and miR-122 expression were changed significantly with the progression of liver fibrosis, of which miR-122 exhibited high read counts enough to be used as a biomarker. The level of exosomal miR-122 decreased as the pathologic fibrosis grade progressed and patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P < 0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis especially in combination with fibrosis-4 score and transient elastography. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker was greatly improved. Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of various fibrosis related proteins. Conclusion: Exosomal miR-122 may serve as a useful non-invasive biomarker for liver fibrosis, especially in patients with non-viral etiologies of chronic liver disease.

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Proteomic profile in the diagnostics of portal hypertension in patients with compensated advanced liver disease

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