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Updated: May 16, 2026

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Lysophospholipid variants in hepatocellular carcinoma
Nicholas J Skill1, Wu Jianmin, Xu Yan
1Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana. nskill@iupui.edu
Background:
The U.S. incidence of hepatocellular carcinoma (HCC) is increasing and is linked to hepatitis C (HepC) infection, alcohol toxicity, and obesity. This manuscript examines lysophosphatidic acid (LPA) variant biosynthesis as a biomarker and potential therapeutic target for HCC.
Methods:
Serum LPA variant levels were determined in patients with HepC ± HCC, alcoholic cirrhosis ± HCC, or nonalcoholic steatohepatitis ± HCC by mass spectroscopy. To clarify the relationship between cancer and LPA variant profiles, LPA variants were evaluated in HepC + HCC patients before and after liver transplantation. Moreover, LPA variant modification of gene expression was also determined in vitro by real-time polymerase chain reaction.
Results:
In patients diagnosed with HCC, 18:2 LPA biosynthesis was decreased, whereas 20:4 LPA biosynthesis and 20:4 LPA:18:2 LPA ratio were increased. Three days after liver transplantation, serum LPA levels and 18:2 LPA:20:4 LPA ratio were significantly reduced in patients with cancer. The 20:4 LPA selectively stimulated LPA receptor and tumor necrosis factor α expression in Hep3B cells, whereas 18:2 LPA did not.
Conclusions:
Serum LPA variant profiles are unique in patients with HCC allowing for the stratification of patients. Moreover, LPA variants impart individual mitogenic properties associated with tumorigenesis that may provide a potential therapeutic target. We envision that LPA profiling may accelerate diagnosis, help stratify patients at high risk of developing cancer, and provide potential targets for chemoprevention.
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