Skip to main content

Advertisement

SpringerLink
Log in

Reduced group IVA phospholipase A2 expression is associated with unfavorable outcome for patients with gastric cancer

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Arachidonic acid metabolic pathway has been implicated in the inflammation-associated tumorigenesis of gastrointestinal cancers. As the rate-limiting enzyme of arachidonic acid production, group IVA phospholipase A2 (PLA2G4A) is hypothesized to play a fundamental role in gastric tumorigenesis as well as cyclooxygenase-2 (COX-2). However, little is known about the expression and role of PLA2G4A in gastric cancer, and the association of PLA2G4A with COX-2 remains to be elucidated. In this study, the mRNA expression of PLA2G4A and COX-2 in 60 pairs of fresh gastric tumors and corresponding adjacent non-cancerous mucosa was detected by using real-time quantitative PCR and the immunostaining of the both proteins in paired samples from 866 gastric cancer patients were assessed by using immunohistochemistry method. The clinicopathological and the prognostic relevance of PLA2G4A and COX-2 expression were determined. The results revealed a significantly reduced expression of PLA2G4A in gastric tumors compared to in non-cancerous tissues, as opposite to the increased expression of COX-2. PLA2G4A was significantly associated with tumor size (P = 0.003), tumor grade (P < 0.001), intestinal type (P = 0.003), T classification (P < 0.001), N classification (P < 0.001), and thereby TNM stage (P < 0.001). PLA2G4A and COX-2 expression were both identified as independent prognostic factors in multivariate Cox model analysis (P = 0.024 for PLA2G4A and P < 0.001 for COX-2). Moreover, the reduced PLA2G4A and increased COX-2 expression was both associated with unfavorable survival for patients with gastric cancer. PLA2G4A might serve as a promising target for future therapeutic approaches to gastric cancer combined with COX-2 inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.

    Article  PubMed  CAS  Google Scholar 

  2. Sethi G, Shanmugam MK, Ramachandran L, Kumar AP, Tergaonkar V. Multifaceted link between cancer and inflammation. Biosci Rep. 2012;32:1–15.

    Article  PubMed  CAS  Google Scholar 

  3. Wang D, Dubois RN. Prostaglandins and cancer. Gut. 2006;55:115–22.

    Google Scholar 

  4. Konturek PC, Kania J, Burnat G, Hahn EG, Konturek SJ. Prostaglandins as mediators of COX-2 derived carcinogenesis in gastrointestinal tract. J Physiol Pharmacol. 2005;56(Suppl 5):57–73.

    PubMed  Google Scholar 

  5. Boland CR, Luciani MG, Gasche C, Goel A. Infection, inflammation, and gastrointestinal cancer. Gut. 2005;54:1321–31.

    Article  PubMed  CAS  Google Scholar 

  6. Wang D, Dubois RN. Eicosanoids and cancer. Nat Rev Cancer. 2010;10:181–93.

    Article  PubMed  CAS  Google Scholar 

  7. Nakanishi M, Rosenberg DW. Roles of cPLA2alpha and arachidonic acid in cancer. Biochim Biophys Acta. 2006;1761:1335–43.

    Article  PubMed  CAS  Google Scholar 

  8. Schaloske RH, Dennis EA. The phospholipase A2 superfamily and its group numbering system. Biochim Biophys Acta. 2006;1761:1246–59.

    Article  PubMed  CAS  Google Scholar 

  9. Leslie CC. Regulation of the specific release of arachidonic acid by cytosolic phospholipase A2. Prostaglandins Leukot Essent Fatty Acids. 2004;70:373–6.

    Article  PubMed  CAS  Google Scholar 

  10. Saukkonen K, Rintahaka J, Sivula A, et al. Cyclooxygenase-2 and gastric carcinogenesis. APMIS. 2003;111:915–25.

    Article  PubMed  CAS  Google Scholar 

  11. Thiel A, Mrena J, Ristimäki A. Cyclooxygenase-2 and gastric cancer. Cancer Metastasis Rev. 2011;30:387–95.

    Article  PubMed  CAS  Google Scholar 

  12. Yu G, Wang J, Chen Y, et al. Overexpression of phosphorylated mammalian target of rapamycin predicts lymph node metastasis and prognosis of Chinese patients with gastric cancer. Clin Cancer Res. 2009;15:1821–9.

    Article  PubMed  CAS  Google Scholar 

  13. Allred DC, Clark GM, Elledge R, et al. Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst. 1993;85:200–6.

    Article  PubMed  CAS  Google Scholar 

  14. Tsoupras AB, Iatrou C, Frangia C, Demopoulos CA. The implication of platelet activating factor in cancer growth and metastasis: potent beneficial role of PAF-inhibitors and antioxidants. Infect Disord Drug Targets. 2009;9:390–9.

    Article  PubMed  CAS  Google Scholar 

  15. Scott KF, Sajinovic M, Hein J, et al. Emerging roles for phospholipase A2 enzymes in cancer. Biochimie. 2010;92:601–10.

    Article  PubMed  CAS  Google Scholar 

  16. Linkous A, Yazlovitskaya E. Cytosolic phospholipase A2 as a mediator of disease pathogenesis. Cell Microbiol. 2010;12:1369–77.

    Article  PubMed  CAS  Google Scholar 

  17. Soydan AS, Tavares IA, Weech PK, Temblay NM, Bennett A. High molecular weight phospholipase A2 and fatty acids in human colon tumours and associated normal tissue. Eur J Cancer. 1996;32A:1781–7.

    Article  PubMed  CAS  Google Scholar 

  18. Osterström A, Dimberg J, Fransén K, Söderkvist P. Expression of cytosolic and group X secretory phospholipase A(2) genes in human colorectal adenocarcinomas. Cancer Lett. 2002;182:175–82.

    Article  PubMed  Google Scholar 

  19. Wendum D, Svrcek M, Rigau V, et al. COX-2, inflammatory secreted PLA2, and cytoplasmic PLA2 protein expression in small bowel adenocarcinomas compared with colorectal adenocarcinomas. Mod Pathol. 2003;16:130–6.

    Article  PubMed  Google Scholar 

  20. Panel V, Boëlle PY, Ayala-Sanmartin J, et al. Cytoplasmic phospholipase A2 expression in human colon adenocarcinoma is correlated with cyclooxygenase-2 expression and contributes to prostaglandin E2 production. Cancer Lett. 2006;243:255–63.

    Article  PubMed  CAS  Google Scholar 

  21. Heasley LE, Thaler S, Nicks M, Price B, Skorecki K, Nemenoff RA. Induction of cytosolic phospholipase A2 by oncogenic Ras in human non-small cell lung cancer. J Biol Chem. 1997;272:14501–4.

    Article  PubMed  CAS  Google Scholar 

  22. Sundarraj S, Kannan S. Immunohistochemical expression of cytosolic phospholipase A2α in non-small cell lung carcinoma. Asian Pac J Cancer Prev. 2010;11:1367–72.

    PubMed  Google Scholar 

  23. Patel MI, Singh J, Niknami M, et al. Cytosolic phospholipase A2-alpha: a potential therapeutic target for prostate cancer. Clin Cancer Res. 2008;14:8070–9.

    Article  PubMed  CAS  Google Scholar 

  24. Zhang S, Du Y, Tao J, Wu Y, Chen N. Expression of cytosolic phospholipase A2 and cyclooxygenase 2 and their significance in human oral mucosae, dysplasias and squamous cell carcinomas. ORL J Otorhinolaryngol Relat Spec. 2008;70:242–8.

    Article  PubMed  CAS  Google Scholar 

  25. Meyer AM, Dwyer-Nield LD, Hurteau GJ, et al. Decreased lung tumorigenesis in mice genetically deficient in cytosolic phospholipase A2. Carcinogenesis. 2004;25:1517–24.

    Article  PubMed  CAS  Google Scholar 

  26. Dong M, Johnson M, Rezaie A, et al. Cytoplasmic phospholipase A2 levels correlate with apoptosis in human colon tumorigenesis. Clin Cancer Res. 2005;11:2265–71.

    Article  PubMed  CAS  Google Scholar 

  27. Dong M, Guda K, Nambiar PR, et al. Inverse association between phospholipase A2 and COX-2 expression during mouse colon tumorigenesis. Carcinogenesis. 2003;24:307–15.

    Article  PubMed  CAS  Google Scholar 

  28. Ilsley JN, Nakanishi M, Flynn C, et al. Cytoplasmic phospholipase A2 deletion enhances colon tumorigenesis. Cancer Res. 2005;65:2636–43.

    Article  PubMed  CAS  Google Scholar 

  29. Soydan AS, Gaffen JD, Weech PK, et al. Cytosolic phospholipase A2, cyclo-oxygenases and arachidonate in human stomach tumours. Eur J Cancer. 1997;33:1508–12.

    Article  PubMed  CAS  Google Scholar 

  30. Lagorce-Pagès C, Paraf F, Wendum D, Martin A, Fléjou JF. Expression of inflammatory secretory phospholipase A2 and cytosolic phospholipase A2 in premalignant and malignant Barrett’s oesophagus. Virchows Arch. 2004;444:426–35.

    Article  PubMed  Google Scholar 

  31. Caiazza F, McCarthy NS, Young L, Hill AD, Harvey BJ, Thomas W. Cytosolic phospholipase A2-α expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours. Br J Cancer. 2011;104:338–44.

    Article  PubMed  CAS  Google Scholar 

  32. Yoo YS, Lim SC, Kim KJ. Prognostic significance of cytosolic phospholipase A2 expression in patients with colorectal cancer. J Korean Surg Soc. 2011;80:397–403.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 30973432 and No. 81000983).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Oncology, Changzheng Hospital, Second Military Medical University, 64 Hetian Road, Shanghai, 200070, China

    Xia Zhang, Lu Gan, Guan-Zhen Yu, Jie-Jun Wang & Xi Wang

  2. Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China

    Qiong Wu, Rui Wang & Zi-Shu Wang

Authors
  1. Xia Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lu Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guan-Zhen Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zi-Shu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jie-Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jie-Jun Wang or Xi Wang.

Additional information

Xia Zhang and Qiong Wu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, X., Wu, Q., Gan, L. et al. Reduced group IVA phospholipase A2 expression is associated with unfavorable outcome for patients with gastric cancer. Med Oncol 30, 454 (2013). https://doi.org/10.1007/s12032-012-0454-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-012-0454-y

Keywords

Search

Navigation