Gut microbiome remodeling across hepatocellular carcinoma progression and transarterial chemoembolization is associated with therapeutic response and prognosis
摘要
Clinical outcomes after transarterial chemoembolization (TACE) for intermediate–to–advanced hepatocellular carcinoma (HCC) are highly variable, and reliable predictive biomarkers are lacking. Although gut microbiota dysbiosis has been implicated in HCC pathogenesis and immunotherapy response, its role in TACE outcomes remains unclear. This study aimed to delineate gut microbiome remodeling across HCC progression and TACE treatment and to evaluate its association with clinical outcomes. Fecal samples were collected from healthy controls (n = 10), newly diagnosed untreated HCC patients (n = 30), post-TACE HCC patients (n = 29), and a longitudinal cohort of TACE-treated patients (n = 56). Gut microbiota profiles were analyzed using 16S rDNA sequencing. Differential taxa, microbial diversity, functional pathways, and survival associations were assessed using bioinformatics and Kaplan–Meier analyses. Gut microbiome composition differed markedly across healthy controls, untreated HCC, and post-TACE patients. Bacteroides abundance progressively decreased, whereas Prevotella_9 increased across disease progression and treatment. Among TACE-treated patients, progressive disease was characterized by higher Prevotella_9 and lower Bacteroides and Ruminococcus abundance, accompanied by significantly reduced microbial diversity. Kaplan–Meier analysis showed that low Prevotella_9 (P = 0.001) and high Bacteroides (P = 0.001) and Faecalibacterium (P = 0.04) were associated with prolonged progression-free survival, while higher Phascolarctobacterium and Veillonella abundance correlated with shorter overall survival. Functional prediction revealed alterations in pathways related to lipid metabolism, carbohydrate metabolism, and immune regulation. Gut microbiome remodeling is closely associated with HCC progression and TACE outcomes. Specific microbial taxa, particularly Bacteroides and Prevotella_9, were associated with therapeutic response and prognosis; however, these findings are exploratory and warrant We hypothesized that specific microbial taxa and metabolic pathways could serve as predictive biomarkers of TACE efficacy and clinical outcomes.