Serum Osteopontin Enhances Hepatocellular Carcinoma Diagnosis and Predicts Anti-PD-L1 Immunotherapy Benefit.

Background: Osteopontin (OPN), a phosphorylated glycoprotein encoded by SPP1, critical in hepatic inflammation and fibrosis, requires further investigation for its role on hepatocellular carcinoma (HCC) and predictive value for anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy responses. Methods: Publicly available datasets were utilized to explore OPN expression in HCC. A retrospective cohort study involving 316 participants, recruited from January 2015 to March 2017. Serum OPN levels were measured by enzyme-linked immunosorbent assay. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, a logistic regression model was developed for early HCC diagnosis. Prospective follow-up was conducted from 2017 to 2024 to evaluate overall survival (OS) and disease-free survival (DFS) using Kaplan-Meier analyses. The survival benefit of anti-PD-L1 immunotherapy for patients with OPN patterns was investigated. Results: Serum OPN levels were significantly elevated in HCC compared to chronic liver disease and healthy individuals (both Conclusion: Serum OPN demonstrates standalone diagnostic value for HCC and enhances conventional biomarker panels when combined with AFP and AST. OPN high pattern identify patients likely to benefit from anti-PD-L1 immunotherapy, suggesting its dual utility as a diagnostic and predictive biomarker.