46 - Inhibiting the FGFR4 Signaling Pathway Suppresses Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma After Transarterial Chemoembolization

Monday, March 31, 2025

12:10 PM – 1:10 PM CT

Location: Music City Center, Expo Poster Area

Poster Presenter(s)

Shen Zhang, MD

Resident doctor
The first affiliated hospital of soochow university, China (People's Republic)

Author/Co-author(s)

hl

han si liang, PhD

Resident doctor
The first affiliated hospital of soochow university, China (People's Republic)
JL

Jia Qing Li, MD

Resident doctor
The first affiliated hospital of soochow university, China (People's Republic)
GX

Gui Li Xu, PhD

Resident doctor
The first affiliated hospital of soochow university, China (People's Republic)
XZ

Xiaoli Zhu, MD, PhD

Chief Physician
The First Affiliated Hospital of Soochow University, China (People's Republic)

Purpose: To investigate the mechanism of Lenvatinib inhibiting epithelial-mesenchymal transition(EMT) in hepatocellular carcinoma after transarterial chemoembolization(TACE).

Materials and Methods: HCC rats were categorized into either TACE alone or TACE combined with Lenvatinib group. EMT-associated proteins were analyzed using bioinformatic databases and validated in vitro using HCC cell lines(Huh7 and SNU-449) and in vivo through nude mouse. Statistical significance was set at P< 0.05 using ANOVA and Pearson correlation.

Results:

Immunohistochemistry analysis post-TACE demonstrated EMT enhancement and PD-L1 upregulation, both attenuated by lenvatinib (P< 0.05). Bioinformatic analysis found a closed correlation between PD-L1 and Snail-1, which is the crucial transcription factor of EMT(P< 0.001). In vitro Transwell assays exhibited that lenvatinib restrained the migration and invasion abilities in Huh7 and SNU-449 cells under hypoxic/starvation condition. PD-L1 overexpression facilitated HCC cells invasion, which lenvatinib suppressed. FGFR4 inhibitor reduced Huh7 migration and invasion. In nude mouse, PD-L1 overexpression decreased E-cadherin, increased Snail-1 expression in HCC tissue, and promoted lung metastasis (P< 0.01), which was reversed by lenvatinib administration or FGFR4 knockdown(P< 0.01).

Conclusion: Inhibiting the FGFR4 signaling pathway suppresses EMT in HCC after TACE.