Hepatocellular carcinoma associated lipid metabolism reprogramming.
BACKGROUND
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high worldwide prevalence and poor prognosis. Previous data, by Affymetrix microarray analysis, has shown a decrease in genes involved in phospholipid catabolism, fatty acid catabolism, choline metabolism, and bile acid metabolism in HCC compared with control tissue. The aim of this study was to better understand metabolic processes in relation to the development of HCC.


METHODS
Tumor, plasma, and bile samples were collected at the time of hepatic resection for HCC. All bile specimens were collected from the gallbladder at the beginning of the case. Normal bile and plasma were collected from patients undergoing cholecystectomy for non-neoplastic disease. Liver biopsy samples were taken from both tumor and adjacent normal tissue. Phospholipid levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and high performance thin layer chromatography (HPTLC).


RESULTS
Targeted phospholipid analysis by HPTLC and ELISA showed a modified choline metabolic profile within the liver, bile, and serum, culminating in an increased synthesis of lysophosphatidic acid (LPA). Choline was significantly increased in tumor tissue; lysophosphatidylcholine (LPC) was increased within bile while LPA was increased in all three biological samples of HCC patients compared with controls. Phosphatidylcholine was not significantly changed.


CONCLUSIONS
HCC is congruent with a reprogramming of choline catabolism and phospholipid metabolism. Increased LPA may provide a potent mitogenic and proliferative microenvironment via autocrine/paracrine activation of high-affinity G-protein-coupled receptors. Additional research is required to better understand the role of these pathways in HCC development.
Skill
Nicholas James
NJ
Department of Surgery, Indiana University, Indianapolis, Indiana 46202, USA. nskill@iupui.edu
Scott
Rachael E
RE
Wu
Jianmin
J
Maluccio
Mary A
MA
D001646:Bile / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics* / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010743:Phospholipids; D043562:Receptors, G-Protein-Coupled; D002794:Choline; C032881:lysophosphatidic acid