Overexpression of Phospholipase A2 Group IIA in Esophageal Squamous Cell Carcinoma and Association with Cyclooxygenase-2 Expression

  • Zhai, Yan-Chun (Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University) ;
  • Dong, Bin (Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Central Laboratory, Peking University Cancer Hospital & Institute) ;
  • Wei, Wen-Qiang (Department of Cancer Epidemiology, Cancer Institute, Peking Union Medical College, Chinese Academy of Medical Science) ;
  • He, Yan (Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University) ;
  • Li, Xin-Qing (Department of Cancer Epidemiology, Cancer Institute, Peking Union Medical College, Chinese Academy of Medical Science) ;
  • Cormier, Robert T. (Department of Biomedical Sciences, University of Minnesota Medical School Duluth) ;
  • Wang, Wei (Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University) ;
  • Liu, Fen (Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University)
  • Published : 2014.11.28


Background: Esophageal cancer is one of the most frequently occurring malignancies and the seventh leading cause of cancer-related deaths in the world. The esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer worldwide. Materials and Methods: Our goal in this study was to detect phospholipase A2 Group IIA (PLA2G2A) and cyclooxygenase-2 (COX-2) immuno-expression in ESCC in a high-risk population in China. Results: Positive expression of PLA2G2A protein was observed in 57.2% (166/290) of the cases, while COX-2 was found in 257 of 290 samples (88.6%), both PLA2G2A and COX-2 being expressed in 153 cases (52.8%), with a significant agreement (Kappa=0.091, p=0.031).Overexpression of PLA2G2A was significantly correlated with the depth of invasion (p=0.001). Co-expression of PLA2G2A and COX-2 not only significantly correlated with the depth of invasion (p=0.004) but also with TNM stage (p=0.04). Conclusions: Our results showed that in patients with ESCC, PLA2G2A overexpression and PLA2G2A co-expression with COX-2 is significantly correlated with advanced stage. The biological role and pathophysiologic regulation of PLA2G2A and COX-2 overexpression in ESCC deserve further investigation.


Supported by : Beijing Natural Science Foundation, National Natural Science Foundation of China, Beijing Municipal Institutions


  1. Cormier RT, Bilger A, Lillich AJ, et al (2000). The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64. Oncogene, 19, 3182-92.
  2. Cormier RT, Hong KH, Halberg RB, et al (1997). Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis. Nat Genet, 17, 88-91.
  3. Cummings BS (2007). Phospholipase $A_2$ as targets for anti-cancer drugs. Biochem Pharmacol, 74, 949-59
  4. Edge SB, Byrd DR, Compton CC, et al., eds (2009). AJCC Cancer Staging Manual. 7nd ed., Springer, New York, 103-15.
  5. Ferri, Fred (2012). Ferri's clinical advisor. 1st ed., Elsevier Mosby, St. Louis, 389-91.
  6. Fijneman RJ, Peham JR, van de Wiel MA, et al (2008). Expression of Pla2g2a prevents carcinogenesis in Muc2-deficient mice. Cancer Sci, 99, 2113-9.
  7. Galecki P, Galecka E, Maes M, et al (2012). The expression of genes encoding for COX-2, MPO, iNOS, and sPLA2-IIA in patients with recurrent depressive disorder. J Affect Disord, 138, 360-6.
  8. Ganesan K, Ivanova T, Wu Y, et al (2008). Inhibition of gastric cancer invasion and metastasis by PLA2G2A, a novel beta-catenin/TCF target gene. Cancer Res, 68, 4277-86.
  9. Gomes TS, Noguti J, Forones NM, et al (2013). Correlation analysis of c-myc, p21 (WAF/CIP1), p53, C-erbB-2 and COX-2 proteins in esophageal squamous cell carcinoma. Pathol Res Pract, 209, 6-9.
  10. Graham DY, Chan FK (2008). NSAIDs, risks, and gastroprotective strategies: current status and future. Gastroenterology, 134, 1240-l6.
  11. Hong KH, Bonventre JC, O'Leary E, et al (2001). Deletion of cytosolic phospholipase A (2) suppresses Apc (Min)-induced tumorigenesis. Proc Natl Acad Sci USA, 98, 3935-9.
  12. Tabriz HM, Olfati G, Ahmadi SA, et al (2013). Cyclooxygenase-2 expression in urinary bladder transitional cell carcinoma and its association with clinicopathological characteristics. Asian Pac J Cancer Prev, 14, 4539-43.
  13. Jiang J, Neubauer BL, Graff JR, et al (2002). Expression of group IIA secretory phospholipase $A_2$ is elevated in prostatic intraepithelial neoplasia and adenocarcinoma. Am J Pathol, 160, 667-71.
  14. Leung SY, Chen X, Chu KM, et al (2002). Phospholipase $A_2$ group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis. Proc Natl Acad Sci USA, 99, 16203-l8.
  15. Li L, Zhao J, Wu Z, et al (2009). Meta-analysis: clinicopathological and prognostic significance of cyclooxygenase-2 expression on oesophageal squamous cell carcinoma. Aliment PharmacolTher, 30, 589-96.
  16. Liu F, Pan K, Zhang X, et al (2006). Genetic polymorphisms of cyclooxygenase-2 (COX-2), expression and risk of gastric cancer and its precursors in a Chinese population. Gastroenterology, 130, 1975-84.
  17. Liu F, Wei WQ, Cormier RT, et al (2014). Association of single nucleotide polymorphisms in the prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes with susceptibility to esophageal squamous cell carcinoma. Asian Pac Cancer Prev, 15, 1797-802.
  18. Lin Y, Totsuka Y, He Y, et al (2013). Epidemiology of esophageal cancer in Japan and China. J Epidemiol, 23, 233-42.
  19. MacPhee M, Chepenik KP, Liddell RA, et al (1995). The secretory phospholipase $A_2$ gene is a candidate for the Mom1 locus, a major modifier of APC Min-induced intestinal neoplasia. Cell, 81, 957-l66.
  20. Martin R, Hernandez M, Ibeas E, et al (2009). Secreted phospholipase A2-IIA modulates key regulators of proliferation on astrocytoma cells. J Neurochem, 111, 988-99.
  21. Mauchley D, Meng X, Johnson T, et al (2010). Modulation of growth in human esophageal adenocarcinoma cells by group IIa secretory phospholipase A (2). J Thorac Cardiovasc Surg, 139, 591-9.
  22. Murakami M, Taketomi Y, Sato H, et al (2011). Secreted phospholipase $A_2$ revisited. J Biochem, 150, 233-55.
  23. Peng L, Zhou Y, Wang Y, et al (2013). Prognostic significance of COX-2 immunohistochemical expression in colorectal cancer: a meta-analysis of the literature. PLoS One, 8, 58891.
  24. Ren P, Zhang JG, Xiu L, et al (2013). Clinical significance of phospholipase $A_2$ group IIA (PLA2G2A) expression in primary resected esophageal squamous cell carcinoma. Eur Rev Med Pharmacol Sci, 17, 752-7.
  25. Savage SA, Abnet CC, Mark SD, et al (2004). Variants of the IL8 and IL8RB genes and risk for gastric cardia adenocarcinoma and esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev, 13, 2251-7.
  26. Scott KF, Sajinovic M, Hein J, et al (2010). Emerging roles for phospholipase $A_2$ enzymes in cancer. Biochimie, 92, 601-10.
  27. Takedo MM (1998). Cyclooxygenase-2 inhibitors in tumorigenesis (Part I). J Natl Cancer Inst, 90, 1529-36.
  28. Wang X, Huang CJ, Yu GZ, et al (2013). Expression of group IIA phospholipase $A_2$ is an independent predictor of favorable outcome for patients with gastric cancer. Hum Pathol, 44, 2020-7.
  29. Xing XF, Li H, Zhong XY, et al (2011). Phospholipase $A_2$ group IIA expression correlates with prolonged survival in gastric cancer. Histopathology, 59, 198-206.
  30. Zhang N, Wen D, Shan B, et al (2011). Clustering and geographic variation of upper gastrointestinal cancers in a high-risk region of esophageal cancer in northern China. Asian Pac J Cancer Prev, 12, 193-8.

Cited by

  1. Prognostic and predictive role of COX-2, XRCC1 and RASSF1 expression in patients with esophageal squamous cell carcinoma receiving radiotherapy vol.13, pp.4, 2017,