Serum angiopoietin-like protein 4 concentration as a predictive biomarker for immunotherapy response in hepatocellular carcinoma
Meng-Wei Lin, Huang-Pin Chen, Chun-Te Lee, Meng-Wei Alan Lin, Chung-Teng Wang, Yi-Tseng Tsai, Hung-Tsung Wu, Hsin-Yu KuoBackground
Elevated serum angiopoietin-like protein 4 (ANGPTL4) levels have been reported in hepatocellular carcinoma (HCC), and they promote tumor aggressiveness and an immunosuppressive tumor microenvironment. However, its association with immunotherapy response in HCC remains unclear.
Objectives
To investigate the relationship among serum ANGPTL4, immunotherapy response and clinical outcomes in patients with unresectable HCC.
Design
This was a retrospective analysis conducted at a single center.
Methods
A total of 70 unresectable HCC patients who received immune checkpoint inhibitor therapy were enrolled. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors. Serum ANGPTL4 concentrations were measured using enzyme-linked immunosorbent assay. Multivariable logistic regression and Cox proportional hazards regression analysis were performed to evaluate associations among serum ANGPTL4 concentration and treatment response, progression-free survival (PFS), and overall survival (OS). Bootstrap resampling was used for internal validation to generate corrected estimates of model accuracy.
Results
Responders exhibited significantly lower baseline serum ANGPTL4 concentrations than non-responders (P = 0.004). Higher serum ANGPTL4 concentrations (odds ratio [OR] = 0.82; P = 0.041), macrovascular invasion (OR = 0.25; P = 0.022), and AFP levels ≥ 400 ng/mL (OR = 0.29; P = 0.038) were independently associated with unfavorable immunotherapy response. Higher serum ANGPTL4 concentrations were also independently associated with shorter PFS (hazard ratio [HR] = 1.10; P = 0.021) and OS (HR = 1.13; P = 0.005).
Conclusion
Lower baseline serum ANGPTL4 concentrations were independently associated with favorable immunotherapy response and improved survival outcomes in unresectable HCC.