CELL INTELLIGENCE · 肿瘤细胞治疗研究

Transcriptomic analyses were performed using public RNA-sequencing datasets of patients with hepatocellular carcinoma receiving anti-PD-L1-based therapy, comparing responders (complete response/partial response) with non-responders (stable disease/progressive disease). Differentially expressed genes and enriched pathways were identified using integrated differential expression and pathway analysis. For validation, RNA-sequencing was performed on institutional tumor samples ( n = 6) underwent. Immunohistochemistry was performed on resected specimens ( n = 9) to evaluate CD8+ tumor-infiltrating lymphocytes and hepcidin protein expression encoded by the HAMP gene. Group comparisons for the pre-specified immunohistochemistry endpoints were analyzed using exact Wilcoxon rank-sum tests with multiplicity control (Holm adjustment).

Analysis of public datasets revealed distinct expression profiles in responders, enriched in immune-related and chemokine signaling pathways. Candidate genes, including HAMP, TAT, and HRG, were upregulated in responders. In institutional samples, HAMP expression was significantly higher in preoperatively treated tumors ( p = 0.001). Immunohistochemistry demonstrated greater CD8+ tumor-infiltrating lymphocyte density (median 36.6 vs. 5.0 cells/high-power field; exact Wilcoxon p = 0.032) and higher HAMP immunoreactive scores (median 4 vs. 0.5; p = 0.032) in responders than in non-responders.

Upregulation of HAMP and hepcidin protein expression, together with increased CD8+ T-cell infiltration, was associated with a favorable response to atezolizumab-bevacizumab in patients with hepatocellular carcinoma. HAMP may serve as a component of a composite biomarker predictive of therapeutic sensitivity, warranting validation in larger, multi-institutional cohorts.