title: Reduced group IVA phospholipase A2 expression is associated with unfavorable outcome for patients with gastric cancer.
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.
authors.affiliation: Department of Oncology, Changzheng Hospital, Second Military Medical University, 64 Hetian Road, Shanghai 200070, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.forename: Guan-Zhen
authors.initials: GZ
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Zi-Shu
authors.initials: ZS
authors.lastname: Wang
authors.forename: Jie-Jun
authors.initials: JJ
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D054513:Group IV Phospholipases A2 / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D054513:Group IV Phospholipases A2