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KMID : 1103920140200010028
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Korean Journal of Hepatology
2014 Volume.20 No. 1 p.28 ~ p.37
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Role of 15-hydroxyprostaglandin dehydrogenase down-regulation on the prognosis of hepatocellular carcinoma
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Yang Jee-Eun
Park Eun-Ji
Lee Hyo-Jeong
Kang Hyo-Jeong
Kim Kang-Mo
Yu Eun-Sil
Lee Dan-Bi
Shim Ju-Hyun
Lim Young-Suk
Lee Han-Chu
Chung Young-Hwa
Lee Yung-Sang
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Abstract
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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.
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KEYWORD
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Hepatocellular carcinoma, 15-hydroxyprostaglandin dehydrogenase, Transfection, Immunohistochemistry, Survival analysis
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