Elucidating sorafenib resistance mechanisms in HCC and discovering bioactive TCM components via bioinformatics and network pharmacology

• Identification of ALB as a central hub gene in sorafenib-resistant HCC and its high-affinity binding with β-sitosterol from Cordyceps sinensis • Revealing a unique resistance-reversal mechanism via the ALB/T4/T3/AKT pathway, distinct from sorafenib's action • Establishing a novel network pharmacology framework bridging TCM and modern oncology for HCC therapy Introduction: Hepatocellular carcinoma (HCC) constitutes approximately 80% of primary liver malignancies, with sorafenib as its first-line therapy often exhibiting limited efficacy due to drug resistance. Aim: This study systematically explored the mechanisms underlying sorafenib resistance and screened potential Traditional Chinese Medicine (TCM) - derived bioactive compounds as candidates for future investigation through integrated bioinformatics and network pharmacology approaches. Materials and methods : Sorafenib resistance – related differentially expressed genes (DEGs) (|log2FC| ≥1, adj. P