Expression of secreted phospholipase A2-Group IIA correlates with prognosis of gastric adenocarcinoma

Zhang,Chengwei; Yu,Haipeng; Xu,Haiyan; Yang,Lanlan

doi:10.3892/ol.2015.3736

Expression of secreted phospholipase A2-Group IIA correlates with prognosis of gastric adenocarcinoma

Authors:
- Chengwei Zhang
- Haipeng Yu
- Haiyan Xu
- Lanlan Yang
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Affiliations: Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China, Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Biliary and Pancreatic Internal Medicine, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
Published online on: September 21, 2015 https://doi.org/10.3892/ol.2015.3736
Pages: 3050-3058

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Abstract

The present study investigated the expression of secretory phospholipase A2-Group IIA (sPLA2-II) in gastric adenocarcinoma, in order to evaluate the correlation between sPLA2‑II expression, and the clinicopathological features and prognosis of patients with gastric adenocarcinoma. Between January 2007 and April 2010, data were collected from 65 patients (44 males, 21 females; age range, 30‑79 years; mean 66.7 ± 10.7 years). All patients exhibited a pathologically confirmed diagnosis of gastric adenocarcinoma. Endoscopic biopsy specimens of normal gastric mucosa from 11 of these patients were used as controls. Patients were subsequently followed‑up at 3‑month intervals, and survival data were recorded until April 2010. Expression of sPLA2‑II in 65 gastric adenocarcinoma and 11 normal gastric mucosa specimens was evaluated via immunohistochemistry. A semi‑quantitative method, consisting of evaluation of staining percentage and intensity, was utilized for immunohistochemical scoring, and the receiver operating characteristic curve method was applied to select a cut‑off score for high and low sPLA2‑II expression. The value of 8 was selected as the cut‑off score, with maximum sensitivity and speciﬁcity. High sPLA2‑II expression was observed in stage III/IV cases (83.3%; 40/48) and poorly differentiated cells (94.1%; 32/34), while sPLA2‑II expression levels were observed to be significantly lower in stage I/II cases (52.9%; 9/17) and well and moderately differentiated cells (54.8%; 17/31; P=0.021 and P<0.001, respectively). There were no significant correlations observed between sPLA2‑II expression and any other clinicopathological parameters, including gender, age, tumor diameter and Helicobacter pylori infection. Patients exhibiting low sPLA2‑II expression experienced significantly improved overall survival (OS) and disease‑free survival (DFS), compared with those exhibiting high sPLA2‑II expression (P=0.043 and P=0.035, respectively). Multivariate analysis confirmed that high sPLA2‑II expression may be an independent prognostic factor for OS [relative risk, 2.849; 95% confidence interval (CI), 1.088‑7.459; P=0.033] and DFS (relative risk, 2.735; 95% CI, 1.104‑6.776; P=0.030) in gastric adenocarcinoma. Therefore, sPLA2‑II may be correlated with the histogenesis of gastric adenocarcinoma, and increased sPLA2‑II expression may be an indicator of poor prognosis.

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1	Rasool S, Rasool V, Naqvi T, Ganai BA and Shah BA: Genetic unraveling of colorectal cancer. Tumour Biol. 35:5067–5082. 2014. View Article : Google Scholar : PubMed/NCBI
2	Arnold CN, Goel A, Blum HE and Boland CR: Molecular pathogenesis of colorectal cancer: Implications for molecular diagnosis. Cancer. 104:2035–2047. 2005. View Article : Google Scholar : PubMed/NCBI
3	Hayee B, Inoue H, Sato H, Santi EG, Yoshida A, Onimaru M, Ikeda H and Kudo SE: Magnification narrow-band imaging for the diagnosis of early gastric cancer: A review of the Japanese literature for the Western endoscopist. Gastrointest Endosc. 78:452–461. 2013. View Article : Google Scholar : PubMed/NCBI
4	Clarke CJ, Forman S, Pritchett J, Ohanian V and Ohanian J: Phospholipase C-delta1 modulates sustained contraction of rat mesenteric small arteries in response to noradrenaline, but not endothelin-1. Am J Physiol Heart Circ Physiol. 295:H826–H834. 2008. View Article : Google Scholar : PubMed/NCBI
5	Samuelsson B: Role of basic science in the development of new medicines: Examples from the eicosanoid field. J Biol Chem. 287:10070–10080. 2012. View Article : Google Scholar : PubMed/NCBI
6	D'Arrigo P and Servi S: Synthesis of lysophospholipids. Molecules. 15:1354–1377. 2010. View Article : Google Scholar : PubMed/NCBI
7	Liang NS and Fang ZW: Platelet phospholipase A₂ and tumor. China Oncol. 12:555–558. 2002.
8	Hamilton JA: Stimulation of macrophage prostaglandin and neutral protease production by phorbol esters as a model for the induction of vascular changes associated with tumor promotion. Cancer Res. 40:2273–2280. 1980.PubMed/NCBI
9	Wang M, Hao FY, Wang JG and Xiao W: Group IIa secretory phospholipase A2 (sPLA2IIa) and progression in patients with lung cancer. Eur Rev Med Pharmacol Sci. 18:2648–2654. 2014.PubMed/NCBI
10	Dikken JL, van de Velde CJ, Gönen M, Verheij M, Brennan MF and Coit DG: The New American Joint Committee on Cancer/International Union Against Cancer staging system for adenocarcinoma of the stomach: Increased complexity without clear improvement in predictive accuracy. Ann Surg Oncol. 19:2443–2451. 2012. View Article : Google Scholar : PubMed/NCBI
11	Berlth F, Bollschweiler E, Drebber U, Hoelscher AH and Moenig S: Pathohistological classification systems in gastric cancer: Diagnostic relevance and prognostic value. World J Gastroenterol. 20:5679–5684. 2014. View Article : Google Scholar : PubMed/NCBI
12	Yousfi MM, el-Zimaity HM, Genta RM and Graham DY: Evaluation of a new reagent strip rapid urease test for detection of Helicobacter pylori infection. Gastrointest Endosc. 44:519–522. 1996. View Article : Google Scholar : PubMed/NCBI
13	Zhu ZH, Sun BY, Ma Y, Shao JY, Long H, Zhang X, Fu JH, Zhang LJ, Su XD, Wu QL, et al: Three immunomarker support vector machines-based prognostic classifiers for stage IB non-small-cell lung cancer. J Clin Oncol. 27:1091–1099. 2009. View Article : Google Scholar : PubMed/NCBI
14	Constantine CE and Wreghitt TG: A rapid micro-agglutination technique for the detection of antibody to Legionella pneumophila serogroup 5. J Med Microbiol. 34:29–31. 1991. View Article : Google Scholar : PubMed/NCBI
15	Situ D, Wang J, Ma Y, Zhu Z, Hu Y, Long H and Rong T: Expression and prognostic relevance of MUC1 in stage IB non-small cell lung cancer. Med Oncol. 28(Suppl 1): S596–S604. 2011. View Article : Google Scholar : PubMed/NCBI
16	Zhao Jiuda, He Juxiang and Geng Paili: PLA2G II A gene in gastric cancer tissues and its significance. Shandong Medical Journal. 46:24–25. 2006.
17	Huhtinen HT, Grönroos JM, Uksila J, Grass DS, Nevalainen TJ and Laine VJ: Experimental Helicobacter felis infection in transgenic mice expressing human group IIA phospholipase A2. Helicobacter. 9:408–416. 2004. View Article : Google Scholar : PubMed/NCBI
18	Huhtinen HT, Grönroos JO, Grönroos JM, Uksila J, Gelb MH, Nevalainen TJ and Laine VJ: Antibacterial effects of human group IIA and group XIIA phospholipase A2 against Helicobacter pylori in vitro. APMIS. 114:127–130. 2006. View Article : Google Scholar : PubMed/NCBI
19	Menschikowski M, Rosner-Schiering A, Eckey R, Mueller E, Koch R and Jaross W: Expression of secretory group IIA phospholipase A(2) in relation to the presence of microbial agents, macrophage infiltrates, and transcripts of proinflammatory cytokines in human aortic tissues. Arterioscler Thromb Vasc Biol. 20:751–762. 2000. View Article : Google Scholar : PubMed/NCBI
20	Pandey R, Misra V, Misra SP, Dwivedi M, Kumar A and Tiwari BK: Helicobacter pylori and gastric cancer. Asian Pac J Cancer Prev. 11:583–588. 2010.PubMed/NCBI
21	Hishida A, Matsuo K, Goto Y and Hamajima N: Genetic predisposition to Helicobacter pylori-induced gastric precancerous conditions. World J Gastrointest Oncol. 15:369–379. 2010. View Article : Google Scholar
22	Fock KM, Talley N, Moayyedi P, Hunt R, Azuma T, Sugano K, Xiao SD, Lam SK, Goh KL, Chiba T, et al: Asia-Pacific Gastric Cancer Consensus Conference: Asia-Pacific consensus guidelines on gastric cancer prevention. J Gastroenterol Hepatol. 23:351–65. 2008. View Article : Google Scholar : PubMed/NCBI
23	Ren P, Zhang JG, Xiu L and Yu ZT: Clinical significance of phospholipase A2 group IIA (PLA2G2A) expression in primary resected esophageal squamous cell carcinoma. Eur Rev Med Pharmacol Sci. 17:752–757. 2013.PubMed/NCBI
24	Jiang J, Neubauer BL, Graff JR, Chedid M, Thomas JE, Roehm NW, Zhang S, Eckert GJ, Koch MO, Eble JN and Cheng L: Expression of group IIA secretory phospholipase A2 is elevated in prostatic intraepithelial neoplasia and adenocarcinoma. Am J Pathol. 160:667–671. 2002. View Article : Google Scholar : PubMed/NCBI
25	Liao Z, Fu X, Liao XS, Wang SQ and Kang GF: The change of serum phospholipase A2 activity and its clinical significance in patient with primary liver cancer. Chongqing Medical Journal. 3:203–204. 2000.(In Chinese).
26	Yamashita S, Ogawa M, Sakamoto K, Abe T, Arakawa H and Yamashita J: Elevation of serum group II phospholipase A2 levels in patients with advanced cancer. Clin Chim Acta. 228:91–99. 1994. View Article : Google Scholar : PubMed/NCBI
27	Cai H, Chiorean EG, Chiorean MV, Rex DK, Robb BW, Hahn NM, Liu Z, Loehrer PJ, Harrison ML and Xu Y: Elevated phospholipase A2 activities in plasma samples from multiple cancers. PLoS One. 8:e570812013. View Article : Google Scholar : PubMed/NCBI
28	Yamashita S, Yamashita J and Ogawa M: Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency. Br J Cancer. 69:1166–1170. 1994. View Article : Google Scholar : PubMed/NCBI
29	Scott KF, Sajinovic M, Hein J, Nixdorf S, Galettis P, Liauw W, de Souza P, Dong Q, Graham GG and Russell PJ: Emerging roles for phospholipase A2 enzymes in cancer. Biochimie. 92:601–610. 2010. View Article : Google Scholar : PubMed/NCBI
30	Yamashita S, Yamashita J, Sakamoto K, Inada K, Nakashima Y, Murata K, Saishoji T, Nomura K and Ogawa M: Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells. Cancer. 71:3058–3064. 1993. View Article : Google Scholar : PubMed/NCBI
31	Kennedy BP, Soravia C, Moffat J, Xia L, Hiruki T, Collins S, Gallinger S and Bapat B: Overexpression of the nonpancreatic secretory group II PLA2 messenger RNA and protein in colorectal adenomas from familial adenomatous polyposis patients. Cancer Res. 58:500–503. 1998.PubMed/NCBI
32	Kudo I and Murakami M: Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat. 68(69): 3–58. 2002. View Article : Google Scholar : PubMed/NCBI
33	Fenard D, Lambeau G, Maurin T, Lefebvre JC and Doglio A: A peptide derived from bee venom-secreted phospholipase A2 inhibits replication of T-cell tropic HIV-1 strains via interaction with the CXCR4 chemokine receptor. Mol Pharmacol. 60:341–347. 2001.PubMed/NCBI
34	Yamashita S, Yamashita J and Ogawa M: Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency. Br J Cancer. 69:1166–1170. 1994. View Article : Google Scholar : PubMed/NCBI
35	Leung SY, Chen X, Chu KM, Yuen ST, Mathy J, Ji J, Chan AS, Li R, Law S, Troyanskaya OG, et al: Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis. Proc Natl Acad Sci USA. 99:16203–16208. 2002. View Article : Google Scholar : PubMed/NCBI
36	Kiyohara H, Egami H, Kako H, Shibata Y, Murata K, Ohshima S, Sei K, Suko S, Kurano R and Ogawa M: Immunohistochemical localization of group II phospholipase A2 in human pancreatic carcinomas. Int J Pancreatol. 13:49–57. 1993.PubMed/NCBI
37	Mannello F, Qin W, Zhu W, Fabbri L, Tonti GA and Sauter ER: Nipple aspirate fluids from women with breast cancer contain increased levels of group IIa secretory phospholipase A2. Breast Cancer Res Treat. 111:209–218. 2008. View Article : Google Scholar : PubMed/NCBI
38	Mauchley D, Meng X, Johnson T, Fullerton DA and Weyant MJ: Modulation of growth in human esophageal adenocarcinoma cells by group IIa secretory phospholipase A(2). J Thorac Cardiovasc Surg. 139:591–599. 2010. View Article : Google Scholar : PubMed/NCBI
39	Fijneman RJ and Cormier RT: The roles of sPLA2-IIA (Pla2g2a) in cancer of the small and large intestine. Front Biosci. 13:4144–4174. 2008. View Article : Google Scholar : PubMed/NCBI
40	Ikegami T, Matsuzaki Y, Fukushima S, Shoda J, Olivier JL, Bouscarel B and Tanaka N: Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells. Hepatology. 41:896–905. 2005. View Article : Google Scholar : PubMed/NCBI
41	Zlobec I, Steele R, Terracciano L, Jass JR and Lugli A: Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol. 60:1112–1116. 2007. View Article : Google Scholar : PubMed/NCBI
42	Liu R, Qi H, Wang J, Wang Y, Cui L, Wen Y and Yin C: Ulinastatin activates the renin-angiotensin system to ameliorate the pathophysiology of severe acute pancreatitis. J Gastroenterol Hepatol. 29:1328–1337. 2014. View Article : Google Scholar : PubMed/NCBI
43	Hughes-Fulford M, Li CF, Boonyaratanakornkit J and Sayyah S: Arachidonic acid activates phosphatidylinositol 3-kinase signaling and induces gene expression in prostate cancer. Cancer Res. 66:1427–1433. 2006. View Article : Google Scholar : PubMed/NCBI