肠道菌群和中晚期肝癌TACE联合靶免治疗预后相关性OA

[Objective]To characterize the features of the gut microbiome and its association with clinical prognosis in patients with intermediate and advanced hepatocellular carcinoma(HCC)treated with transcatheter arterial chemoembolization(TACE)combined with targeted therapy and immunotherapy.[Methods]This retrospective study enrolled patients with intermediate and advanced HCC who received TACE combined with targeted therapy and immunotherapy at the First Affiliated Hospital of Sun Yat-sen University from February 2025 to July 2025.Baseline clinical data and fecal samples were collected from all enrolled patients before the index hospitalization and treatment.Patients were stratified using two independent criteria:① a good-prognosis group and a poor-prognosis group,based on whether progression-free survival(PFS)reached 6 months;② a response group and a non-response group,based on tumor response to the first TACE assessed by the modified Response Evaluation Criteria in Solid Tumors(mRECIST).Metagenomic sequencing was performed on fecal samples.Bioinformatic analysis was conducted to evaluate the diversity and compositional differences of intestinal bacterial and fungal communities between groups in each stratification,and to screen for prognosis-associated characteristic microbial taxa.[Results]A total of 61 patients met the inclusion criteria.Analysis of α-diversity and β-diversity showed no statistically significant differences in bacterial and fungal diversity between groups under either stratification strategy(P＞0.05).At the bacterial level,Lactobacillus johnsonii(prognosis stratification:P=0.048;response stratification:P=0.043),Bifidobacterium dentium(prognosis stratification:P=0.004;response stratification:P=0.030)and Clostridioides difficile(prognosis stratification:P=0.017;response stratification:P=0.016)were significantly enriched in both the good prognosis group and the response group.At the fungal level,Cryptococcus decaguttatus(P=0.045),Puccinia striiformis(P=0.002),and Kwoniella quercicola(P=0.015)were enriched in the good-prognosis group;Kwoniella bestiolae(P=0.037)was enriched in the response group;and Akanthomyces muscarius(P=0.024)was enriched in the non-response group.Survival analysis based on the common differential bacterial abundance in both groupings showed a significant correlation between the abundance of Bifidobacterium dentium and patient prognosis.[Conclusion]Differences in the gut microbiota are associated with the prognosis of patients with intermediate and advanced HCC treated with TACE combined with targeted therapy and immunotherapy.Bifidobacterium dentium may serve as a potential predictive biomarker for the efficacy of this combination regimen,and represents a potential intervention target to modulate treatment response.Differences in gut fungal communities are also potentially associated with the prognosis of intermediate and advanced HCC patients receiving TACE combined with targeted therapy and immunotherapy.