To dissect the mechanisms underlying sorafenib resistance in vivo and further elucidate the detailed mechanisms of accelerated PGC1β degradation in sorafenib resistance in HCC, we constructed a subcutaneous sorafenib-resistant HCC mouse model using HCCLM3 cells (Fig. 4a), according to previous studies.12,25,33 Whole-proteome analysis by mass spectrometry found 80 differentially expressed proteins between parental and resistant tumors (p < 0.05; Fig. 4b). The gene discussed is PPARGC1B; the disease is hepatocellular carcinoma.