Clinical and Molecular Hepatology

"Survival analysis"

Original Articles

Hepatic neoplasm

Role of 15-hydroxyprostaglandin dehydrogenase down-regulation on the prognosis of hepatocellular carcinoma: Jee Eun Yang, Eunji Park, Hyo Jeong Lee, Hyo Jeong Kang, Kang Mo Kim, Eunsil Yu, Danbi Lee, Ju Hyun Shim, Young-Suk Lim, Han Chu Lee, Young-Hwa Chung, Yung Sang Lee; Clin Mol Hepatol 2014;20(1):28-37.
Published online March 26, 2014; DOI: https://doi.org/10.3350/cmh.2014.20.1.28

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.

Citations

Citations to this article as recorded by

The tumor suppressor role and epigenetic regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in cancer and tumor microenvironment (TME)
SubbaRao V. Tulimilli, Medha Karnik, Anjali Devi S. Bettadapura, Olga A. Sukocheva, Edmund Tse, Gowthamarajan Kuppusamy, Suma M. Natraj, SubbaRao V. Madhunapantula
Pharmacology & Therapeutics.2025; 268: 108826. CrossRef
15-Keto prostaglandin E2 induces heme oxygenase-1 expression through activation of Nrf2 in human colon epithelial CCD 841 CoN cells
Jeong-Eun Lee, Xiancai Zhong, Ja-Young Lee, Young-Joon Surh, Hye-Kyung Na
Archives of Biochemistry and Biophysics.2020; 679: 108162. CrossRef
The prostanoid pathway contains potential prognostic markers for glioblastoma
Alexandros Theodoros Panagopoulos, Renata Nascimento Gomes, Fernando Gonçalves Almeida, Felipe da Costa Souza, José Carlos Esteves Veiga, Anna Nicolaou, Alison Colquhoun
Prostaglandins & Other Lipid Mediators.2018; 137: 52. CrossRef

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Survival Analysis for Patients with Hepatocellular Carcinoma according to Stage, Liver Function and Treatment Modalities: Kyung Woo Park , Joong Won Park , Sang Hyung Cho , Young Il Kim , Seong Hoon Kim , Hong Suk Park , Woo Jin Lee , Sang Jae Park , Dae Young Kim , Eun Kyoung Hong , Chang; Korean J Hepatol 2006;12(1):41-54.

Abstract
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Background/Aims
Hepatocellular carcinoma (HCC) is 3rd leading cause of cancer in Korea and the prognosis for HCC patients is poor. For assessing the present treatment outcome, this study analyzed the three-year survival rate (3-YSR) and the prognostic factors for patients with HCC in Korea. Methods: Between November 2000 and December 2003, 905 patients with HCC who were diagnosed and treated at the National Cancer Center Korea were enrolled in this study. The clinical variables, tumor characteristics and survival periods were analyzed. Results: The mean age of all patients was 56.2±10.3 years and 732 (80.9%) patients were male (M:F=4.2:1). 508 (56.1%) patients died and the median survival period was 15.3 months. The overall 3-YSR of the patients with modified UICC stage I, II, III, IVa and IVb were 67.4%, 65.2%, 30.7%, 9.0% and 5.0%, respectively. The modified UICC stage could not differentiate stage I from II, and stage IVa from IVb, on the 3-YSR. The 3-YSR of the Child-Pugh class A patients with modified UICC stage I or II was 85.4% by surgical resection and it was 69.6% by transcatheter chemoembolization (TACE), respectively (P= .461), and those values for patients with stage III were 49.2% and 36.8%, respectively (P=.081). As compared with systemic chemotherapy or conservative therapy, TACE increased the survival rate more for the Child-Pugh class A patients with stage IV. The independent prognostic factors were serum AFP, portal vein thrombosis, the Child-Pugh classification and the stage of HCC. Conclusions: This follow-up study will be helpful in assessing the results of treatments for HCC and it will provide data for the establishment of a more effective treatment strategy. (Korean J Hepatol 2006;12:41-54)

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Evaluation of Predictive Value of Okuda, TNM, CLIP and JIS Staging Systems for Hepatocellular Carcinoma Patients: Sung-Wook Lee, M.D., Sang-Young Han, M.D., Kyoung-Tae Kim, M.D., Yang-Hyun Baek, M.D., In Young Koh, M.D., Byoung-Hee Kim, M.D., Eun-Hee Park, M.D., Jin-Seok Jang, M.D., Myung-Hwan Roh, M.D, Jong Cheol Choi, M.D.; Korean J Hepatol 2007;13(2):196-207.

Abstract
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Background/Aims
The aims of this study were to validate the prognostic value of the JIS score for HCC and to compare discriminatory ability and predictive power with other staging systems such as Okuda, TNM and CLIP. Methods: We analyzed the clinical records of 210 patients who were diagnosed as HCC from 2000 to 2002. Univariate and multivariate survival analyses were done to find out factors to affect survival. To validate prognostic value of those staging systems, survival curve was obtained and analyzed by the Kaplan-Meier’s method, and to compare discriminatory ability and predictive power, Homogeneity LR X² test and AIC score were used. Results: The median survival was 19.5 months (19.1±14.9). The number of patients and 3-year survival rate for those staging systems were Okuda 1(126, 57.7%), 2(63, 9.0%) and 3(21, 0.0%) (p<0.001); TNM I (34, 63.1%), II (71, 59.4%), III (50, 22.4%), IV-A (6, 14.3%) and IV-B (1, 6.5%) (p<0.001); CLIP 0 (79, 68.5%), 1 (39, 34.2%), 2 (36, 16.7%), 3 (25, 20.0%), 4 (18, 5.1%), 5 (9, 11.1%) and 6 (4, 0.0%) (p<0.001) and JIS 0 (26, 78.9%), 1 (65, 65.3%), 2 (43, 21.9%), 3 (40, 25, 8.0%) and 5 (11, 2.0%)(p<0.001) in univariate analysis using Kaplan-Meier analysis. Homogeneity LR X² test showed more stratification power in JIS (Okuda, 102.8; TNM, 128.2; CLIP, 148.4 and JIS, 185.6) and AIC score showed superior predictive power in JIS system (Okuda, 1228.5; TNM, 1130.3; CLIP, 1117.1 and JIS, 1093.6). Conclusions: The proposed JIS system is useful system to predict survival of HCC patients. The discriminate ability of the JIS score is much better than other staging systems and has better prognostic predictive power compared to other staging systems. (Korean J Hepatol 2007;13:196-207)