Japan Digestive Disease Week 2025
International Session (Symposium)1 (JSH, JSGE)
October 30, 9:30–12:00, Room 11 (Portopia Hotel South Wing Topaz)
IS-S1-5_H
Spatial Transcriptomic Profiling Identifies a Predictive Biomarker for Non-Response to Atezolizumab Plus Bevacizumab in HCC
- 1
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University
- 2
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
Aim
Atezolizumab plus bevacizumab (Atezo+Bev) is standard therapy for advanced hepatocellular carcinoma (HCC). However, no established biomarkers predict efficacy before treatment. This study aimed to identify predictive biomarkers for non-response.
Methods
We conducted spatial transcriptomic analysis on pre-treatment HCC biopsy specimens from six patients and post-treatment surgical specimens from two (responders [R]: CR/PR/SD; non-responders [NR]: PD) to identify factors linked to PD. We then analyzed pre-treatment serum samples from 35 Atezo+Bev-treated patients to assess the association between proteins identified by VISIUM and response, followed by validation in an independent cohort of 60 patients.
Results
Spatial transcriptomic analysis (VISIUM) of post-treatment specimens revealed uniformly high expression of cytokine X in NR tumors, with similar findings in pre-treatment biopsies. Xenium5K showed strong interactions between M2 macrophages and cytokine X-high HCC cells, while VISIUM HD identified adhesion receptor-mediated interactions. Pre-treatment serum cytokine X levels were significantly elevated in NR (p = 0.012). ROC analysis established a cutoff (96.5 pg/mL), and high cytokine X levels were associated with shorter progression-free survival in the validation cohort (p = 0.004).
Conclusion
Cytokine X, identified through spatial transcriptomics, was significantly associated with PD when measured in pre-treatment serum, suggesting its potential as a predictive biomarker for Atezo+Bev efficacy in advanced HCC.
Atezolizumab plus bevacizumab (Atezo+Bev) is standard therapy for advanced hepatocellular carcinoma (HCC). However, no established biomarkers predict efficacy before treatment. This study aimed to identify predictive biomarkers for non-response.
Methods
We conducted spatial transcriptomic analysis on pre-treatment HCC biopsy specimens from six patients and post-treatment surgical specimens from two (responders [R]: CR/PR/SD; non-responders [NR]: PD) to identify factors linked to PD. We then analyzed pre-treatment serum samples from 35 Atezo+Bev-treated patients to assess the association between proteins identified by VISIUM and response, followed by validation in an independent cohort of 60 patients.
Results
Spatial transcriptomic analysis (VISIUM) of post-treatment specimens revealed uniformly high expression of cytokine X in NR tumors, with similar findings in pre-treatment biopsies. Xenium5K showed strong interactions between M2 macrophages and cytokine X-high HCC cells, while VISIUM HD identified adhesion receptor-mediated interactions. Pre-treatment serum cytokine X levels were significantly elevated in NR (p = 0.012). ROC analysis established a cutoff (96.5 pg/mL), and high cytokine X levels were associated with shorter progression-free survival in the validation cohort (p = 0.004).
Conclusion
Cytokine X, identified through spatial transcriptomics, was significantly associated with PD when measured in pre-treatment serum, suggesting its potential as a predictive biomarker for Atezo+Bev efficacy in advanced HCC.
- Index Term 1: hepatocellular carcinoma
- Index Term 2: biomarker