Related Experiment Video
Updated: Sep 15, 2025

Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
Androgen receptor promotes arachidonic acid metabolism and angiogenic microenvironment in AFP-negative hepatocellular
Zhilong Lin1, Xiaofei Liu2, Houwei Wang1
1Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Abstract:
Alpha-fetoprotein (AFP) is a classic biomarker for hepatocellular carcinoma (HCC). AFP-positive HCC (AFP+ HCC) has been intensively investigated; however, the genomic, transcriptomic and microenvironmental characteristics of AFP-negative HCC (AFP- HCC) remain to be deciphered. Here we show that tumors display mild differences in genetic alterations between AFP- HCC and AFP+ HCC patients, while AFP- HCC exhibits hyperactive arachidonic acid metabolism. Furthermore, the transcription activity of androgen receptor (AR) is significantly increased in AFP- HCC and plays a positive regulatory role in arachidonic acid metabolism and its metabolite 11,12-epoxyeicosatrienoic acid (11,12-EET). The tumor-derived 11,12-EET exhibits high affinity for EGFR that promotes the migration and tube formation of endothelial cells in vitro. Combination of lenvatinib and bicalutamide (an AR antagonist) enhances the therapeutic efficacy for AFP- HCC. Overall, we uncover the AR-mediated hyperactive arachidonic acid metabolism in AFP- HCC, and reveal AR-11,12-EET-EGFR axis-induced angiogenesis, providing a promising strategy of combined AR antagonist with lenvatinib for AFP- HCC treatment.
Related Concept Videos
Regulation of Angiogenesis and Blood Supply
Mechanism of Angiogenesis
The Tumor Microenvironment
Mitogens and the Cell Cycle
mTOR Signaling and Cancer Progression
The mTOR pathway or the...

