Plasma Vascular Endothelial Growth Factor‐A Identified by Proximity Extension Assay Predicts Early Progression in Hepatocellular Carcinoma Treated With Atezolizumab and Bevacizumab
Hepatology Research, 2025
Tajima K., Miuma S., Sasaki R., Kanda Y., Matsuo S., Shimakura A., Takahashi K., Nakao Y., Fukushima M., Haraguchi M., Ozawa E., Ichikawa T., Nakao K., Miyaaki H.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Oncology Hepatology Immunotherapy | Patient Stratification | Plasma |  Olink Target 96 |
Abstract
Aim
Hepatocellular carcinoma (HCC), a major cause of cancer death, highlights the need for biomarkers predicting early progressive disease (PD) under atezolizumab/bevacizumab (Atezo/Bev) therapy. We used the proximity extension assay (PEA) to identify plasma biomarkers linked to early PD.
Methods
This study included 47 patients with unresectable HCC treated with Atezo/Bev, divided into derivation ( n = 27) and validation ( n = 20) cohorts. To identify plasma biomarkers for early PD, 92 cytokines were measured by PEA; enzyme‐linked immunosorbent assays (ELISA) were then used to determine key protein cutoffs in derivation. Cutoff validity was confirmed in validation.
Results
PEA showed vascular endothelial growth factor (VEGF)‐A, angiopoietin‐2 (ANGPT2), and Tie‐2 were elevated in early PD cases. ELISA confirmed significantly higher levels in early PD versus nonearly PD (VEGF‐A: 78.3 pg/mL vs. 53.2 pg/mL and p = 0.002; ANGPT2: 18.4 ng/mL vs. 12.7 ng/mL and p = 0.007; and Tie‐2: 24.5 ng/mL vs. 17.6 ng/mL and p = 0.009). After establishing cutoff values for each protein, multivariate logistic regression analysis incorporating clinical background identified VEGF‐A as the sole independent predictor of early PD (cutoff: 73.9 pg/mL, OR: 40.00, and p = 0.006). The predictive value of VEGF‐A for early PD was evaluated in the validation cohort. With a cutoff of 73.9 pg/mL, early PD occurred in 21.4% and 83.3% of the low ( n = 14) and high VEGF‐A groups ( n = 6), respectively ( p = 0.018).
Conclusions
Plasma VEGF‐A levels were identified as a significant biomarker for early PD in individuals with HCC receiving Atezo/Bev therapy.