Lysophospholipid variants in hepatocellular carcinoma

N. Skill, Wu Jianmin, Yan Xu, Zhenweng Zhao, Alfred J. Tector, Mary Maluccio

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalJournal of Surgical Research
Volume182
Issue number2
DOIs
StatePublished - Jun 15 2013

Fingerprint

Lysophospholipids
Hepatocellular Carcinoma
Hepatitis C
lysophosphatidic acid
Liver Transplantation
Serum
Lysophosphatidic Acid Receptors
Alcoholic Liver Cirrhosis
Neoplasms

Keywords

  • Autotaxin
  • Hepatocellular carcinoma
  • Lysophospholipids
  • Mass spectroscopy
  • Reprogramming
  • Transplant

ASJC Scopus subject areas

  • Surgery

Cite this

Lysophospholipid variants in hepatocellular carcinoma. / Skill, N.; Jianmin, Wu; Xu, Yan; Zhao, Zhenweng; Tector, Alfred J.; Maluccio, Mary.

In: Journal of Surgical Research, Vol. 182, No. 2, 15.06.2013, p. 241-249.

Research output: Contribution to journalArticle

Skill, N. ; Jianmin, Wu ; Xu, Yan ; Zhao, Zhenweng ; Tector, Alfred J. ; Maluccio, Mary. / Lysophospholipid variants in hepatocellular carcinoma. In: Journal of Surgical Research. 2013 ; Vol. 182, No. 2. pp. 241-249.
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