Impact of anesthesia‐related genes on prognosis and tumor microenvironment in hepatocellular carcinoma: A comprehensive analysis

Abstract Hepatocellular carcinoma (HCC), renowned for its bleak prognosis and high recurrence rates, necessitates innovative strategies for prognosis assessment and therapeutic intervention. In this pursuit, we systematically investigated the influence of anesthesia‐related genes (ANARGs) on HCC outcomes. Leveraging data from The Cancer Genome Atlas (TCGA), our study scrutinized RNA sequencing data and clinical profiles from 374 HCC patients alongside 50 non‐tumor liver samples to unravel ANARG expression patterns and their clinical relevance. Employing consensus clustering, we segregated HCC samples into two distinct subtypes based on ANARG profiles, unveiling significant survival disparities between them. Further differential expression analysis pinpointed pivotal genes and pathways distinguishing these subtypes, notably implicating lipid metabolism and the MTOR signaling pathway in HCC pathogenesis. A prognostic model, comprising five key ANARGs (DAGLA, CYP26B, HAVCR, G6PD and AKR1B), exhibited robust predictive capability for patient outcomes, validated across independent patient cohorts. Furthermore, immune infiltration analysis uncovered a nuanced interplay between ANARG expression and the tumor immune microenvironment, spotlighting variations in immune cell infiltration and function across the identified HCC subtypes. This comprehensive analysis underscores not only the prognostic significance of ANARGs in HCC but also their potential to modulate the tumor microenvironment, providing novel insights for tailoring anesthetic management and therapeutic strategies in HCC care. Our findings advocate for a more integrative approach to HCC management, amalgamating molecular profiling with traditional clinical parameters to refine patient stratification and personalize treatment strategies.