PROZ Associated with Sorafenib Sensitivity May Serve as a Potential Target to Enhance the Efficacy of Combined Immunotherapy for Hepatocellular Carcinoma

Targeted combined immunotherapy has significantly improved the prognosis of patients with advanced hepatocellular carcinoma and has now become the primary treatment for advanced hepatocellular carcinoma. However, some patients still have poor efficacy or are resistant to treatment. The further exploration of molecular markers related to efficacy or finding molecular targets to increase efficacy is an urgent problem that needs to be resolved. In this research, we found that PROZ was a gene related to KDR expression that had significantly low expression in cancer tissue by analyzing the differential genes of cancer tissue and adjacent tissue and the intersection of KDR-related genes in hepatocellular carcinoma. The correlation analysis of clinical data showed that the low expression of PROZ was significantly correlated with the poor prognosis of hepatocellular carcinoma, and further studies found that PROZ was closely related to the expression of p-ERK and VEGFR2 in hepatocellular carcinoma. In addition, intracellular detection also showed that the expression of p-ERK increased and VEGFR2 expression decreased after PROZ interference, and PROZ downregulation with increased p-ERK and decreased VEGFR2 was also detected in sorafenib-resistant strains. At the same time, our analysis found that PROZ was negatively correlated with genes related to immunotherapy efficacy such as CD8A, CD274 and GZMA, and was also negatively correlated with T-cell infiltration in tumor tissue. Conclusion: PROZ is a gene related to the prognosis of hepatocellular carcinoma and it is closely related to the efficacy of sorafenib and immunotherapy. It may serve as a potential molecular target to improve the efficacy of targeted combined immunotherapy.