Association Analysis Between Gut Microbiota and Prognosis in Patients with Intermediate-to-advanced Hepatocellular Carcinoma Treated with TACE Combined with Targeted Therapy and Immunotherapy

LIU Hang; ZHU Bowen; FAN Wenzhe; LI Jiaping; WU Yanqin

doi:10.11714/jsysu.med.YX20260040

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Association Analysis Between Gut Microbiota and Prognosis in Patients with Intermediate-to-advanced Hepatocellular Carcinoma Treated with TACE Combined with Targeted Therapy and Immunotherapy

Academic Frontiers\：Gut Microbiota and Barrier Function | 更新时间：2026-05-25

- Association Analysis Between Gut Microbiota and Prognosis in Patients with Intermediate-to-advanced Hepatocellular Carcinoma Treated with TACE Combined with Targeted Therapy and Immunotherapy
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 47, Issue 3, Pages: 397-408(2026)
- 作者机构：
  
  中山大学附属第一医院肿瘤介入科，广东广州 510080
- 作者简介：
  
  WU Yanqin； Email： wuyq73@mail.sysu.edu.cn
- 基金信息：
- DOI：10.11714/jsysu.med.YX20260040
  CLC： R735.7
- Received：14 March 2026，
  
  Revised：2026-04-23，
  
  Accepted：23 April 2026，
  
  Published：20 May 2026
- 稿件说明：
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刘航,朱博文,范文哲等.肠道菌群和中晚期肝癌TACE联合靶免治疗预后相关性[J].中山大学学报（医学科学版）,2026,47(03):397-408.

LIU Hang,ZHU Bowen,FAN Wenzhe,et al.Association Analysis Between Gut Microbiota and Prognosis in Patients with Intermediate-to-advanced Hepatocellular Carcinoma Treated with TACE Combined with Targeted Therapy and Immunotherapy[J].Journal of Sun Yat-sen University(Medical Sciences),2026,47(03):397-408.
刘航,朱博文,范文哲等.肠道菌群和中晚期肝癌TACE联合靶免治疗预后相关性[J].中山大学学报（医学科学版）,2026,47(03):397-408. DOI： 10.11714/jsysu.med.YX20260040.

LIU Hang,ZHU Bowen,FAN Wenzhe,et al.Association Analysis Between Gut Microbiota and Prognosis in Patients with Intermediate-to-advanced Hepatocellular Carcinoma Treated with TACE Combined with Targeted Therapy and Immunotherapy[J].Journal of Sun Yat-sen University(Medical Sciences),2026,47(03):397-408. DOI： 10.11714/jsysu.med.YX20260040.

摘要

目的

探讨中晚期肝细胞癌（HCC）患者经动脉化疗栓塞（TACE）联合靶免治疗后肠道菌群组的特征及与预后的关联。

方法

本研究回顾性收集2025年2月至2025年7月就诊中山大学附属第一医院并接受过TACE联合靶免治疗的中晚期肝细胞癌患者临床资料，采集患者本次入院治疗前的粪便样本。根据无进展生存期（PFS）是否达到6个月，分为预后好组与预后差组；按照修正后实体瘤疗效评价标准（mRECIST）评估首次TACE术后是否缓解，分为应答组与无应答组。采用宏基因组测序技术对粪便菌群测序，通过生信分析判断两组肠道细菌与真菌群落的多样性、组成差异，筛选预后相关的特征性菌群。

结果

共计61例患者符合标准。α多样性及β多样性分析，两种分组方式组间细菌、真菌多样性均无统计学差异（

＞0.05）。在细菌层面，约氏乳杆菌（预后分组

=0.048，应答分组

=0.043）、齿双歧杆菌（预后分组

=0.004，应答分组

=0.030）和艰难梭菌（预后分组

=0.017，应答分组

=0.016）在预后好组和应答组中均显著富集。真菌层面，十齿隐球菌（

=0.045）、条锈菌（

=0.002）、嗜树克沃尼埃拉菌（

=0.015）在预后好组中富集；叶斑病菌（

=0.037）在应答组中富集；毒蝇钩霉菌（

=0.024）在无应答组中富集。按照两种分组的共同差异菌丰度分别进行生存分析，结果显示齿双歧杆菌的丰度与患者预后存在显著关联。

结论

肠道菌群的差异同中晚期肝癌TACE联合靶免治疗的预后相关，齿双歧杆菌可能作为评估联合治疗疗效的潜在预测指标或影响其疗效的潜在干预途径。肠道真菌群的差异可能与中晚期肝癌TACE联合靶免治疗的预后相关。

Abstract

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 （

＞ 0.05）. At the bacterial level， Lactobacillus johnsonii （prognosis stratification：

=0.048； response stratification：

=0.043）， Bifidobacterium dentium （prognosis stratification：

=0.004； response stratification：

=0.030） and Clostridioides difficile （prognosis stratification：

=0.017； response stratification：

=0.016） were significantly enriched in both the good prognosis group and the response group. At the fungal level， Cryptococcus decaguttatus （

=0.045）， Puccinia striiformis （

=0.002）， and Kwoniella quercicola （

=0.015） were enriched in the good‑prognosis group； Kwoniella bestiolae （

=0.037） was enriched in the response group； and Akanthomyces muscarius （

=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.

关键词

Keywords

references

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