Ann Surg Treat Res.  2014 Jun;86(6):302-308. 10.4174/astr.2014.86.6.302.

Relationship between 15-hydroxyprostaglandin dehydrogenase and gastric adenocarcinoma

• Kang JH
• Kang SH
• Seo SH
• Shin JH
• An MS
• Ha TK
• Bae KB
• Kim TH
• Choi CS
• Oh SH
• Kang MS
• Kim KH

• KMID: 2167107
• DOI: http://doi.org/10.4174/astr.2014.86.6.302

Abstract

PURPOSE
Prostaglandin E2 (PGE2) is a contributory carcinogen in gastric adenocarcinoma. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catabolizes PGE2 by oxidizing its 15(s)-hydroxy group. The aim of this study was to investigate the expression of 15-PGDH in gastric adenocarcinoma tissue and the relationship between 15-PGDH expression and clinicopathologic features of gastric adenocarcinoma.
METHODS
Ninety-nine patients who underwent surgical resection for gastric adenocarcinoma between January 2007 and December 2007 were enrolled and evaluated retrospectively.
RESULTS
In 62 patients (62.6%), 15-PGDH expression was lower in gastric adenocarcinoma tissue than in nonneoplastic tissue. Regarding the relationship between 15-PGDH expression and clinicopathological features, 15-PGDH expression was significantly lower in tissues with poor differentiation (P = 0.002), advanced T stage (P = 0.0319), a higher number of lymph node metastases (P = 0.045), lymphatic invasion (P = 0.031), and vascular invasion (P = 0.036).
CONCLUSION
15-PGDH expression was associated with a subset of clinicopathologic features such as differentiation grade, T stage, lymphatic invasion, and vascular invasion.

Keyword

Gastric neoplasms; 15-Hydroxyprostaglandin dehydrogenase; Differentiation; Staging

MeSH Terms

Adenocarcinoma*
Dinoprostone
Humans
Lymph Nodes
Neoplasm Metastasis
Oxidoreductases*
Retrospective Studies
Stomach Neoplasms
Dinoprostone
Oxidoreductases

Figure

• 

  Fig. 1 Immunohistochemical stain for 15-hydroxyprostaglandin dehydronase (15-PGDH). Normal gastric glands express 15-PGDH (A, ×100). Gastric cancer cells show variable expression of 15-PGDH: loss of expression (B, ×100), preserved expression (C, ×100), and overexpression (D, ×100).

Reference

1. Gupta RA, Dubois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 2001; 1:11–21.

2. Wang D, Dubois RN. Prostaglandins and cancer. Gut. 2006; 55:115–122.

3. Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004; 56:387–437.

4. Eisinger AL, Prescott SM, Jones DA, Stafforini DM. The role of cyclooxygenase-2 and prostaglandins in colon cancer. Prostaglandins Other Lipid Mediat. 2007; 82:147–154.

5. Nam KT, Hahm KB, Oh SY, Yeo M, Han SU, Ahn B, et al. The selective cyclooxygenase-2 inhibitor nimesulide prevents Helicobacter pylori-associated gastric cancer development in a mouse model. Clin Cancer Res. 2004; 10:8105–8113.

6. Salzberg DJ, Weir MR. COX-2 inhibitors and cardiovascular risk. Subcell Biochem. 2007; 42:159–174.

7. Farooq M, Haq I, Qureshi AS. Cardiovascular risks of COX inhibition: current perspectives. Expert Opin Pharmacother. 2008; 9:1311–1319.

8. Tai HH, Cho H, Tong M, Ding Y. NAD+-linked 15-hydroxyprostaglandin dehydrogenase: structure and biological functions. Curr Pharm Des. 2006; 12:955–962.

9. Wolf I, O'Kelly J, Rubinek T, Tong M, Nguyen A, Lin BT, et al. 15-hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast cancer. Cancer Res. 2006; 66:7818–7823.

10. Ding Y, Tong M, Liu S, Moscow JA, Tai HH. NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer. Carcinogenesis. 2005; 26:65–72.

11. Backlund MG, Mann JR, Holla VR, Buchanan FG, Tai HH, Musiek ES, et al. 15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. J Biol Chem. 2005; 280:3217–3223.

12. Yan M, Rerko RM, Platzer P, Dawson D, Willis J, Tong M, et al. 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers. Proc Natl Acad Sci U S A. 2004; 101:17468–17473.

13. Tong M, Tai HH. Synergistic induction of the nicotinamide adenine dinucleotide-linked 15-hydroxyprostaglandin dehydrogenase by an androgen and interleukin-6 or forskolin in human prostate cancer cells. Endocrinology. 2004; 145:2141–2147.

14. Tatsuwaki H, Tanigawa T, Watanabe T, Machida H, Okazaki H, Yamagami H, et al. Reduction of 15-hydroxyprostaglandin dehydrogenase expression is an independent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma. Cancer Sci. 2010; 101:550–558.

15. Liu Z, Wang X, Lu Y, Han S, Zhang F, Zhai H, et al. Expression of 15-PGDH is downregulated by COX-2 in gastric cancer. Carcinogenesis. 2008; 29:1219–1227.

16. Yoo NJ, Jeong EG, Lee SH, Lee SH. Expression of 15-hydroxyprostaglandin dehydrogenase, a COX-2 antagonist and tumour suppressor, is not altered in gastric carcinomas. Pathology. 2007; 39:174–175.

17. Jang TJ, Ji YS, Jung KH. Decreased expression of 15-hydroxyprostaglandin dehydrogenase in gastric carcinomas. Yonsei Med J. 2008; 49:917–922.

18. Thiel A, Ganesan A, Mrena J, Junnila S, Nykanen A, Hemmes A, et al. 15-hydroxyprostaglandin dehydrogenase is down-regulated in gastric cancer. Clin Cancer Res. 2009; 15:4572–4580.

19. Liu Z, Wang X, Lu Y, Du R, Luo G, Wang J, et al. 15-Hydroxyprostaglandin dehydrogenase is a tumor suppressor of human gastric cancer. Cancer Biol Ther. 2010; 10:780–787.

20. Lou LH, Jing DD, Lai YX, Lu YY, Li JK, Wu K. 15-PGDH is reduced and induces apoptosis and cell cycle arrest in gastric carcinoma. World J Gastroenterol. 2012; 18:1028–1037.

21. Song HJ, Myung SJ, Kim IW, Jeong JY, Park YS, Lee SM, et al. 15-hydroxyprostaglandin dehydrogenase is downregulated and exhibits tumor suppressor activity in gastric cancer. Cancer Invest. 2011; 29:257–265.

22. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th ed. New York: Springer;2010.

23. Ristimaki A, Honkanen N, Jankala H, Sipponen P, Harkonen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res. 1997; 57:1276–1280.

24. Murata H, Kawano S, Tsuji S, Tsuji M, Sawaoka H, Kimura Y, et al. Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenterol. 1999; 94:451–455.

25. Lim HY, Joo HJ, Choi JH, Yi JW, Yang MS, Cho DY, et al. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. Clin Cancer Res. 2000; 6:519–525.

26. Jang TJ. Expression of proteins related to prostaglandin E2 biosynthesis is increased in human gastric cancer and during gastric carcinogenesis. Virchows Arch. 2004; 445:564–571.

27. Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: review and considerations for future directions. Ann Surg. 2005; 241:27–39.

28. Tanaka A, Watanabe T, Okuno K, Yasutomi M. Perineural invasion as a predictor of recurrence of gastric cancer. Cancer. 1994; 73:550–555.

29. Kooby DA, Suriawinata A, Klimstra DS, Brennan MF, Karpeh MS. Biologic predictors of survival in node-negative gastric cancer. Ann Surg. 2003; 237:828–835.

30. Kim CH, Jang SW, Kang SH, Kim SW, Song SK. The significance of lymphatic, venous, and neural invasion as prognostic factors in patients with gastric cancer. J Korean Gastric Cancer Assoc. 2005; 5:113–119.