ArticleLiver international : official journal of the International Association for the Study of the Liver2025
Serum Proteomic Profile Based on the TGF-β Pathway Stratifies Risk of Hepatocellular Carcinoma.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Large-Scale Plasma Proteomics Enhances Prediction of Liver-Related Events Among Individuals With Prediabetes and Type 2 Diabetes: A Prospective Cohort Study in the UK Biobank.Diabetes, obesity & metabolism · 2026Article
- Serum Proteomic Profile Based on the TGF-β Pathway Stratifies Risk of Hepatocellular Carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
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20 authors.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths, primarily due to late-stage diagnosis. In this multicenter study, our goal is to identify functional biomarkers that stratify the risk of HCC in patients with cirrhosis (CP) for early diagnosis.
methodsFive thousand and eight serum proteins (Somascan) were analysed in Cohort A (477 CP, including 125 HCC). Clustering analysis of the TGF-β pathway-associated protein signature was performed in a longitudinal, prospective Cohort B (312 CP, in which 18 cases developed HCC over a 5-year follow-up period). Next, a multivariable prediction model was built using logistic regression analysis of cross-sectional data from a matched subgroup (n = 328, Cohort C). Model performance was 10-fold cross-validated across the entire Cohort A (n = 477).
resultsLongitudinal follow-up analysis revealed that patients with elevated TGF-β-related protein signature displayed a five-fold increased risk of developing HCC (9.68% vs. 1.91%). Compared to cirrhosis, serum MSTN, TGFBR2, and AFP levels raised in HCC were validated by ELISA (n = 200, odds ratio = 1.4-2.9, p < 0.05). In Cohort C, 88 proteins were significantly altered in HCC compared to cirrhosis (p < 0.05). The six-protein panel (TGFBR2, MSTN, AFP, COL18A1, GLUL, TP63) displayed a strong performance in the matched cohort C (AUC 0.87, sensitivity 0.88, specificity 0.72), alongside four clinical factors (Age, Sex, BMI, Bilirubin). A 10-fold cross-validation demonstrated a mean AUC of 0.86 in cohort A, with strong predictive power in obese/MASLD/ALD-related patients (AUCs: 0.862-0.921).
conclusionsThe mechanism-based panel effectively stratifies HCC risk in cirrhotic patients, underscoring the need for Phase II/III validation.
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