Identification Of Aberrant Serum Proteins In HBV-Related Decompensated Cirrhosis By Itraq-Based Quantitative Proteomics

Background:Hepatitis B virus (HBV) related decompensated liver cirrhosis (DLC) is a global health problem, especially in developing countries. The current prognostic criteria for HBV-DLC are Child and MELD scores, yet both of them have significant limitations. We aim to search for novel prognostic biomarkers of HBV-related DLC patients.Methods:The serum samples of patients with HBV-related diseases (chronic hepatitis b, compensated liver cirrhosis, and DLC), and health controls were analysed by an isobaric tagging for relative and absolute quantification (iTRAQ) based quantitative proteomic analysis. The candidate proteins aberrantly expressed in HBV-related DLC patients were further validated by ELISA and Western blot. Potential candidate proteins were selected for further valuation in new clinical cohort.Results:In total,437 unique proteins were identified.21 of them were aberrantly expressed in HBV-DLC group compared with non-DLC groups, including 18 down-regulated proteins and 3 up-regulated proteins. After bioinformatics analysis and literature evaluation, Transferrin and SERPINA1 were selected for further validation. Serum levels of transferrin and SERPINA1 measured by ELISA confirmed the robustness of proteomic results, both of which decreased with the disease progression. ROC analysis found that transferrin had more desirable predictive power than SERPINA1 to differentiate DLC patients from non-DLC patients, which implied that transferrin was more likely associated with the prognosis of HBV-DLC. Thus, the association of transferrin with mortality was further investigated. It was observed that low transferrin level was associated with increasing risk of mortality in HBV-related DLC patients (p<0.01). The predictive performance of transferrin was comparable with MELD score (AUC:0.80 vs 0.72, p= 0.13).Conclusion:Serum transferrin might be an associated with the mortality of HBV-related DLC patients. Our findings might suggest a satisfactory feasibility of iTRAQ-based proteomic approach in discovering the prognostic biomarkers for HBV-related DLC patients.