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Clin Mol Hepatol. 2014 Mar;20(1):28-37. doi: 10.3350/cmh.2014.20.1.28. Epub 2014 Mar 26.

Role of 15-hydroxyprostaglandin dehydrogenase down-regulation on the prognosis of hepatocellular carcinoma.

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  • 1Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 2Department of Pathology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

BACKGROUND/AIMS:

The role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients.

METHODS:

The expression of 15-PGDH in HCC cell lines and resected HCC tissues was investigated, and the correlation between 15-PGDH expression and HCC cell-line proliferation and patient survival was explored.

RESULTS:

The interleukin-1-β-induced suppression of 15-PGDH did not change the proliferation of PLC and Huh-7 cells in the MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The induction of 15-PGDH by transfection in HepG2 cells without baseline 15-PGDH expression was suppressed at day 2 of proliferation compared with empty-vector transfection, but there was no difference at day 3. Among the 153 patients who received curative HCC resection between 2003 and 2004 at our institution, 15-PGDH expression was observed in resected HCC tissues in 56 (36.6%), but the 5-year survival rate did not differ from that of the remaining 97 non-15-PGDH-expressing patients (57.1% vs 59.8%; P=0.93). Among 50 patients who exhibited baseline 15-PGDH expression in adjacent nontumor liver tissues, 28 (56%) exhibited a reduction in 15-PGDH expression score in HCC tissues, and there was a trend toward fewer long-term survivors compared with the remaining 22 with the same or increment in their 15-PGDH expression score in HCC tissues.

CONCLUSIONS:

The prognostic significance of 15-PGDH down-regulation in HCC was not established in this study. However, maintenance of 15-PGDH expression could be a potential therapeutic target for a subgroup of HCC patients with baseline 15-PGDH expression in adjacent nontumor liver tissue.

KEYWORDS:

15-hydroxyprostaglandin dehydrogenase; Hepatocellular carcinoma; Immunohistochemistry; Survival analysis; Transfection

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