(Phospho)-proteomic characterization of longitudinal biopsies from HCC patients treated with sorafenib

ABSTRACT: Tumor response rates to targeted therapy are generally low. This poses an urgent medical need to identify molecular mechanisms that determine responsiveness, to inform drug development and therapy. Here, we performed a proteomics and phospho-proteomics (p)proteomics analysis on longitudinal tumor biopsies from eight hepatocellular carcinoma (HCC) patients treated with sorafenib. Three of the patients were responders (group R) and five were nonresponders (group NR). Importantly, the patients clustered by therapy response based on proteomics and p-proteomics data. NR tumors showed increased EMT, glycogen storage, splicing and mitochondrial translation, and decreased carbohydrate metabolism. Furthermore, resistance did not correlate with mTOR signaling but with increased MAPK and decreased AMPK pathway activity. Additionally, phosphorylation of uncharacterized sites (p-sites) in NOTCH pathway components might promote resistance. Our findings suggest potential novel biomarkers for sorafenib-resistant HCC.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Hepatocellular Carcinoma

SUBMITTER: Eva Dazert  

LAB HEAD: Michael N. Hall

PROVIDER: PXD028593 | Pride | 2026-04-27

REPOSITORIES: Pride