title: Higher LPA2 and LPA6 mRNA Levels in Hepatocellular Carcinoma Are Associated with Poorer Differentiation, Microvascular Invasion and Earlier Recurrence with Higher Serum Autotaxin Levels.
abstract: Hepatocellular carcinoma (HCC) commonly develops in patients with liver fibrosis; in these patients, the blood levels of lysophosphatidic acid (LPA) and its generating enzyme autotaxin (ATX) increase with the liver fibrosis stage. We aimed to examine the potential relevance of ATX and LPA in HCC. Fifty-eight HCC patients who underwent surgical treatment were consecutively enrolled in the study. Among the LPA receptors in HCC, higher LPA2 mRNA levels correlated with poorer differentiation, and higher LPA6 mRNA levels correlated with microvascular invasion, which suggested a higher malignant potential of HCC with increased LPA2 and LPA6 expression. In patients with primary HCC, neither LPA2 nor LPA6 mRNA levels were associated with recurrence. However, when serum ATX levels were combined for analysis as a surrogate for plasma LPA levels, the cumulative intra-hepatic recurrence rate was higher in patients in whom both serum ATX levels and LPA2 or LPA6 mRNA levels were higher than the median. However, the mRNA level of phosphatidic acid-selective phospholipase A1ɑ, another LPA-generating enzyme, in HCC patients was not associated with pathological findings or recurrence, even in combination with the expression of LPA receptors. Higher LPA2 mRNA levels were associated with poorer differentiation, and higher LPA6 levels were associated with microvascular invasion in HCC; both became a risk factor for recurrence after surgical treatment when combined with increased serum ATX levels. ATX and LPA receptors merit consideration as therapeutic targets of HCC.
authors: Department of Gastroenterology, The University of Tokyo, Tokyo, Japan.
authors: Kenichiro
authors: K
authors: Enooku
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan.
authors: Baasanjav
authors: B
authors: Uranbileg
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan.
authors: Hitoshi
authors: H
authors: Ikeda
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan.
authors: Makoto
authors: M
authors: Kurano
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan.
authors: Masaya
authors: M
authors: Sato
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan.
authors: Hiroki
authors: H
authors: Kudo
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan.
authors: Harufumi
authors: H
authors: Maki
authors: Department of Gastroenterology, The University of Tokyo, Tokyo, Japan.
authors: Kazuhiko
authors: K
authors: Koike
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan.
authors: Kiyoshi
authors: K
authors: Hasegawa
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan.
authors: Norihiro
authors: N
authors: Kokudo
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan.
authors: Yutaka
authors: Y
authors: Yatomi
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000098:blood supply / Q000473:pathology*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000098:blood supply / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010727:Phosphoric Diester Hydrolases / Q000097:blood*; D012333:RNA, Messenger / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*; D000099189:Lysophospholipase D
chemical_list: D010727:Phosphoric Diester Hydrolases; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D