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Background and Aims: This study investigated the long-term prognosis and clinical course of patients who survived for more than 5 years after hepatocellular carcinoma (HCC) diagnosis., Methods: This retrospective cohort study used data from the Korean National Health Insurance Service database. A total of 35,348 subjects newly diagnosed with HCC between January 2008 and December 2010 were followed up until December 2018., Results: A total of 11,514 (32.6%) survived for 5 years after diagnosis of HCC among 35,348 patients diagnosed with HCC. Long-term survivors (≥ 5 years) had a higher proportion of females, younger age, more frequent aetiology of hepatitis B virus, less frequent liver cirrhosis, diabetes mellitus and hypertension, and received curative treatment more frequently than nonsurvivors (< 5 years). The additional 1-, 3- and 5-year cumulative survival probabilities were 90.7%, 77.6% and 68.4% respectively. Patients who underwent curative treatment as the first treatment for HCC showed a higher additional 5-year cumulative survival probabilities than those treated with noncurative therapy (74.5% vs. 64.2%). Among the long-term survivors, 44.4% underwent HCC retreatment 5 years after HCC diagnosis. The additional 5-year cumulative survival probability was 54.9% in the HCC retreatment group. The overall 5- and 10-year cumulative probabilities of second primary malignancies in long-term survivors were 15.36% and 27.54% respectively. The most frequent second primary malignancy was prostate cancer, followed by colorectal and pancreatic cancers., Conclusion: Our study highlights that a significant proportion of patients with HCC achieve long-term survival beyond 5 years, with favourable outcomes associated with curative treatments., (© 2025 John Wiley & Sons Ltd.)

Backgrounds/aims: Hepatocellular carcinoma (HCC) is characterized by high recurrence and mortality, necessitating the identification of reliable biomarkers. In this study, we aimed to identify the predictive gene signatures for HCC recurrence and evaluate the efficiency of GULP PTB domain-containing engulfment adaptor 1 (GULP1) as a predictive and diagnostic marker and therapeutic target for HCC., Methods: We analyzed genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases via least absolute shrinkage and selection operator Cox regression and 10-fold cross-validation, leading to the development of a 15-gene risk score model, which was validated using three independent datasets. Serum GULP1 and α-fetoprotein levels were assessed to determine the diagnostic accuracy of the model. Using clinical cohorts and patient sera, GULP1 roles were examined, and functional assays in vitro and in vivo were used to evaluate its effects on cell growth, epithelial-mesenchymal transition (EMT), ADP-ribosylation factor 6 activation, and β-catenin signaling., Results: Our newly developed risk-score model accurately predicted recurrent HCC in all datasets. Among the 15 genes in the risk score model, GULP1 was overexpressed in patients with HCC and independently predicted HCC recurrence. Its expression modulation influenced cell growth and EMT, with observed effects on ADP-ribosylation factor 6 activation and β-catenin signaling pathways., Conclusions: GULP1 is a crucial biomarker for HCC, serving as a non-invasive diagnostic and predictive tool. It also plays key roles in HCC progression. Our findings highlight the potential use of GULP1 in treatment strategies targeting EMT and HCC recurrence to improve the personalized care and patient outcomes.