Clin Cancer Res: ST6GAL1, a new serum biomarker for liver cancer driven by Levardinib's susceptible FGF19!

Hepatocellular carcinoma (HCC) has the characteristics of high genetic heterogeneity between tumors.
Two multi-target tyrosine kinase inhibitors (TKI), lenvatinib and sorafenib, are used as standard chemotherapy drugs for patients with advanced liver cancer, but there is no clear stratification strategy due to the lack of effective biomarkers.
, the purpose of this study is to explore HCC biomarkers that indicate sensitivity to levatinib.
researchers screened liver cancer-driven genes associated with TKI susceptivity using a new mouse model of liver cancer.
evaluated a candidate biomarker in the human liver cancer cell line.
then used mass spectrometrology to screen proteins secreted by liver cancer cells.
the correlation between serum and tumor levels of candidate biomarkers and total survival in patients with liver cancer.
PFS studies in patients with high or low FGF19 levels of HCC or low ST6GAL1 levels of HCC showed that levatinib selectively eliminated tumor cells that expressed FGF19, while soraphinib eliminated tumor cells that expressed MET and NRAS.
in HCC cell line, FGF19 levels are associated with levatinib sensitivity, and inhibiting FGF19 eliminates lovatinib sensitivity.
long-term exposure to levatinib liver cancer cells is resistant to levatinib, FGF19 expression is reduced, but FGF19 re-expression can make it sensitive to levatinib.
, FGF19 is a biomarker of levatinib's susceptible to liver cancer.
Serum ST6GAL is a biomarker proteomics and secretion group analysis of Levatini susceptible HCC confirmed that ST6GAL1 is a tumor source secretion protein in liver cancer cells that is regulated by FGF19.
Serum ST6GAL1 levels in patients with liver cancer were positively related to tumor FGF19 expression.
for patients with high serum ST6GAL1 levels of liver cancer treated with TKI, the survival rate of levatinib treatment was significantly higher than that of soraphinib.
, serum ST6GAL may be a new biomarker for HCC driven by FGF19, which identifies Levardinib's susceptibleness.