ArticleClinical proteomics2021
Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan.
Article in Clinical proteomics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Redefining Liver Transplantation Indications for Hepatic Malignancies in the Era of Precision Transplant Oncology: An Up-to-Date Narrative Review.Journal of clinical medicine · 2026Review
- The Role of Galectin-3 in Liver Inflammation and Fibrosis.Journal of inflammation research · 2026Review
- Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar Cholangiocarcinoma.Transplantation direct · 2025Article
- MPCD Index for Hepatocellular Carcinoma Patients Based on Mitochondrial Function and Cell Death Patterns.International journal of molecular sciences · 2024Article
- Hedgehog components are overexpressed in a series of liver cancer cases.Scientific reports · 2024Article
- DeepRTAlign: toward accurate retention time alignment for large cohort mass spectrometry data analysis.Nature communications · 2023Article
- Retinoids in the Pathogenesis and Treatment of Liver Diseases.Nutrients · 2022Review
- Glycosylation-related molecular subtypes and risk score of hepatocellular carcinoma: Novel insights to clinical decision-making.Frontiers in endocrinology · 2022Article
- M2-like tumor-associated macrophage-related biomarkers to construct a novel prognostic signature, reveal the immune landscape, and screen drugs in hepatocellular carcinoma.Frontiers in immunology · 2022Article
- The Role of Chronic Liver Diseases in the Emergence and Recurrence of Hepatocellular Carcinoma: An Omics Perspective.Frontiers in medicine · 2022Review
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsLiver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches.
methodsPatients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry.
resultsSeventy-nine proteins and 636 genes were significantly differentially expressed in HCC tumors with subsequent recurrence (p < 0.05). Univariate survival analysis identified Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) gene (HR = 0.084, 95%CI 0.01-0.68, p = 0.0152), ALDH1A1 protein (HR = 0.039, 95%CI 0.16-0.91, p = 0.03), Galectin 3 Binding Protein (LGALS3BP) gene (HR = 7.14, 95%CI 1.20-432.96, p = 0.03), LGALS3BP protein (HR = 2.6, 95%CI 1.1-6.1, p = 0.036), Galectin 3 (LGALS3) gene (HR = 2.89, 95%CI 1.01-8.3, p = 0.049) and LGALS3 protein (HR = 2.6, 95%CI 1.2-5.5, p = 0.015) as key dysregulated analytes in recurrent HCC. In concordance with our proteome findings, HCC recurrence was linked to decreased ALDH1A1 and increased LGALS3 protein expression by Western Blot. LGALS3BP protein expression was validated in 29 independent HCC samples.
conclusionsSignificantly increased LGALS3 and LGALS3BP gene and protein expression on explant were associated with post-transplant recurrence, whereas increased ALDH1A1 was associated with absence of recurrence in patients transplanted for HCC beyond Milan criteria. This combined proteomic/transcriptomic signature could help in predicting HCC recurrence risk and guide post-transplant surveillance.
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