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AFP/PIVKA-II double-positive status indicates a high-risk subtype of hepatocellular carcinoma in liver transplantation: retrospective cohort study and phosphoproteome evaluation

Year: 2025

Type: article

Abstract: INTRODUCTION: Liver transplantation (LT) is one of the therapeutic options for hepatocellular carcinoma (HCC). α-fetoprotein (AFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II) serologic levels are commonly used in monitoring HCC and have been reported to correlate with LT prognosis. This study aimed to evaluate the overall survival (OS) and tumor-free survival (TFS) after LT in HCC recipients with different preoperative AFP and PIVKA-II status, and to profile HCC molecular characteristics based on phosphoproteome. METHODS: HCC patients undergoing LT from 2015 to 2022 were identified in a clinical multicenter database of the Chinese Liver Transplant Registry. HCC recipients with different AFP and PIVKA-II statuses (A + P +, A-P-, A + P-, A-P +) were compared after propensity score matching. Meanwhile, we collected 6 pairs of paired tumors and adjacent normal tissues to characterize the HCC samples using 4D label-free quantitative proteome and phosphoproteome-based approaches. RESULTS: A total of 798 HCC patients were enrolled in the study according to the screening criteria. The maximum tumor diameter was the largest in A + P +, while the opposite was true for A-P- (p<0.0001). Portal infiltration was up to 25.93% in A + P + . After propensity score matching, there were significant differences in OS (p = 0.020) and TFS (p = 0.003) between the four groups. A + P + and A-P- were the worst and best OS of the four groups, respectively, with the same trend in TFS. For A + P +, the Number of tumor nodules and Intraoperative blood loss were independent risk factors for OS. The number of tumor nodules and Portal vein invasion were independent risk factors for TFS. We mapped the molecular profile of differential gene expression, biological functions, cellular metabolism, and the mTOR pathway in A + P + and A-P- HCC. CONCLUSION: HCC patients with double-positive AFP and PIVKA-II had higher tumor aggressiveness, as well as poorer OS and TFS after LT, while the opposite was true for the double-negative group. The two types of HCC exhibited unique phosphoproteome characterization. For A + P +, monitoring and mitigating their risk factors may improve patients' prognosis.

Source: International Journal of Surgery

DOI: 10.1097/js9.0000000000004101