Prognostic and predictive value ofphospho-c-Jun expressionin hepatocellular carcinoma patients treated with sorafenib

Abstract

Aim: Hepatocellular carcinoma (HCC) is a highly lethal malignancy with limited treatment options at advanced stages. Sorafenib, a multikinase inhibitor, remains a key systemic therapeutic agent; however, treatment response varies significantly among patients. This study aimed to investigate phospho-c-Jun (PCJ) expression as a potential biomarker for sorafenib resistance and its association with survival outcomes in HCC patients. Methods: This retrospective study analyzed 32 HCC patients who received first-line sorafenib therapy between September 2020 and January 2021. Immunohistochemical analysis was performed to determine nuclear phospho-c-Jun expression levels. Patients were categorized based on H-score (>= 87.5 vs <87.5) and staining intensity. Survival outcomes were analyzed using Kaplan-Meier curves and Cox regression analysis. Results: Patients with high PCJ expression (>= 87.5 H-score) had significantly shorter median overall survival (5 months) compared to those with low PCJ expression (18 months, p=0.013). Similarly, patients with high staining intensity (+3) had worse prognosis (3.25 months) compared to those with low staining intensity (17.6 months, p=0.030). Univariate analysis confirmed the prognostic significance of PCJ expression; however, this significance was lost in multivariate analysis, likely due to limited sample size. Conclusion: Elevated PCJ expression is associated with poor response to sorafenib and reduced survival in HCC patients. These findings suggest that PCJ expression could serve as a predictive biomarker for sorafenib response. Further validation in larger cohorts is necessary; however, targeting the c-Jun N-terminal kinase pathway may be a potential therapeutic strategy to overcome sorafenib resistance. This study highlights the importance of molecular profiling in HCC.