Clinical and prognosis relevance of COX-2 expression in Tunisian patients with primary gastric adenocarcinoma

Abstract

Inflammation and hormonal signalling induce the cyclooxygenase-2 (COX-2) expression in various human cancers including Gastric Cancer (GC). GC remains among the human malignancies diagnosticated at advanced tumor stage and thus having a poor prognosis. COX-2 is a key protein in cancer progression which is involved in proliferation, invasion, and metastasis of tumor cells. The aim of this study was to investigate the expression of COX-2 and its association with clinico-patholocigal parameters and survival in Tunisian GC patients and to correlate COX-2 expression with others cancer-related proteins. The immunohistochemistry was used to study the expression of COX-2 on 93 patients with gastric adenocarcinoma. Our results show that COX-2 immunostaining is negative to weak in 51.6%, moderate in 33.3%, and intense in 15.1% of tumor tissues. The expression of COX-2 associated significantly with tumor differentiation (p = 0.003), and histological type (p = 0.039). Furthermore, lack of COX-2 expression is significantly associated with 1-year (p= 0.005), 2-years (p= 0.000), and 5-years (p= 0.042) relapse free survival. In addition, Cox regression model, revealed that metastasis (p= 0.014), tumor site (p= 0.013), histotype (p = 0.02), and COX-2 expression (p = 0.003) are independent factors for prognosis. Regarding the relationship between COX-2 and cancer related proteins, we found that COX-2 expression is positively associated with APC (p = 0.006), and P53 (p = 0.026), supporting a cross link between these proteins in gastric carcinogenesis. Our findings emphasize the importance of COX-2 as a potential marker of tumor progression and prognosis in GC, and that the inhibition of COX-2 activity may have a therapeutic benefit in GC.