The association between retinol metabolic activity and the risk of hepatocellular carcinoma: an analysis based on bulk RNA sequencing and mendelian randomization 

Abstract Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with a 5-year survival rate still below 20%. Alterations in the levels of metabolites involved in retinol metabolism (RM) have been observed during HCC progression. However, the precise mechanisms underlying the involvement of RM-related genes in HCC development remain elusive. In this study, we conducted comprehensive bulk RNA sequencing analysis using publicly available databases and identified significant enrichment of retinol metabolism pathways in HCC. Furthermore, through Mendelian randomization analysis, we elucidated the causal relationship between retinol metabolism and HCC development. Subsequently, employing clustering analysis based on RM-related genes and utilizing univariate Cox proportional hazards regression, we constructed a prognostic risk model for HCC patients. Finally, our investigation into RDH16—a pivotal gene implicated in RM disorders—unveiled its potential functional role. Collectively, these findings highlight the diagnostic and prognostic value of distinct features associated with retinol metabolism for identifying HCC patients who would benefit from timely treatment interventions and achieve optimal prognosis.