Higher LPA2 and LPA6 mRNA Levels in Hepatocellular Carcinoma Are Associated with Poorer Differentiation, Microvascular Invasion and Earlier Recurrence with Higher Serum Autotaxin Levels

Autor: Kazuhiko Koike, Masaya Sato, Yutaka Yatomi, Baasanjav Uranbileg, Kiyoshi Hasegawa, Hitoshi Ikeda, Hiroki Kudo, Kenichiro Enooku, Norihiro Kokudo, Makoto Kurano, Harufumi Maki
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Pathology
Physiology
lcsh:Medicine
Gene Expression
Neovascularization
chemistry.chemical_compound
0302 clinical medicine
Lysophosphatidic acid
Medicine and Health Sciences
Receptors
Lysophosphatidic Acid
lcsh:Science
Receptor
Multidisciplinary
Neovascularization
Pathologic
Liver Diseases
Liver Neoplasms
Cell Differentiation
Hematology
Middle Aged
Body Fluids
Blood
Oncology
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Liver Fibrosis
lipids (amino acids
peptides
and proteins)
Female
Autotaxin
medicine.symptom
Anatomy
Research Article
medicine.medical_specialty
Carcinoma
Hepatocellular
Surgical and Invasive Medical Procedures
Gastroenterology and Hepatology
Biology
Carcinomas
Blood Plasma
03 medical and health sciences
Extraction techniques
Gastrointestinal Tumors
Carcinoma
medicine
Genetics
Humans
RNA
Messenger
Risk factor
Pathological
Differentiated Tumors
Aged
Phosphoric Diester Hydrolases
lcsh:R
Cancers and Neoplasms
Biology and Life Sciences
Hepatocellular Carcinoma
medicine.disease
Fibrosis
digestive system diseases
RNA extraction
Research and analysis methods
030104 developmental biology
chemistry
Cancer research
lcsh:Q
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 9, p e0161825 (2016)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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