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Updated: May 12, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Plasma interleukin-8 as a predictive biomarker for tyrosine kinase inhibitor response in advanced hepatocellular
Sujin Kim1,2,3, Hye Ri Ahn1, Hui Gyeong Kim1
1Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
Background And Aim:
Hepatocellular carcinoma (HCC) is the predominant primary liver cancer and third leading cause of cancer-related death. Despite improvements in overall survival (OS), those in HCC-specific survival rates remain modest. Tyrosine kinase inhibitors (TKIs) are crucial first-line HCC treatments when immune checkpoint inhibitors are unsuitable. To identify plasma biomarkers predicting the therapeutic response to TKIs in patients with HCC.
Methods:
Pre-treatment plasma samples from 60 patients with advanced HCC treated with sorafenib or lenvatinib were analyzed using targeted proteomics. Differentially expressed proteins were identified based on the treatment response (P < 0.05).
Results:
Plasma levels of metalloproteinase 12 and vascular endothelial growth factor A were elevated in patients with progressive disease compared with those with partial response or stable disease, correlating with shorter progression-free survival (PFS) and OS. Among patients with PFS ≥ 12 months, C-C motif chemokine ligand 20, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 5, fibroblast growth factor 2, interleukin (IL)-7, IL-8, IL-18, latency-associated peptide transforming growth factor beta 1, and mucin 16 expressions were significantly upregulated, with IL-8 (CXCL8) levels demonstrating the highest predictive accuracy (area under the receiver operating characteristic = 0.91) and prognostic power for PFS (hazard ratio; HR = 2.97, P = 0.0015) and OS (HR = 3.64, P = 0.001). CXCL8 expression was predominantly localized in tumor-associated myeloid cells and enriched in epithelial-mesenchymal transition- and immune modulation-related pathways, highlighting its importance in the tumor microenvironment.
Conclusions:
Elevated plasma IL-8 levels are strongly associated with poor outcomes in patients with advanced HCC undergoing TKI treatment, suggesting a potential role for IL-8 in guiding TKI therapeutic decisions and identifying high-risk patients.
