Five different classes of methylation behaviors were found: (1) genes methylated in GC only (GSTP1 and RASSF1A); (2) genes showing low methylation frequency (<12%) in CG, IM, and GA, but significantly higher methylation frequency in GC (COX-2, hMLH1, and p16); (3) a gene with low and similar methylation frequency (8.8-21.3%) in four-step lesions (MGMT); (4) genes with high and similar methylation frequency (53-85%) in four-step lesions (APC and E-cadherin); and (5) genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP3).
Cyclo-oxygenase (COX) profile predicts prognosis of gastric cancer; COX-2 positive tumors are more often aggressive, and COX-2 suppression is protective against gastric cancer.
Subdistribution hazard ratio (SHR) of GC with statins was calculated by competing risk regression with propensity score (PS) analysis matching 19 variables (age, sex, comorbidities and other drug usage including proton pump inhibitors, non-steroidal anti-inflammatory drugs, aspirin, cyclooxygenase-2 inhibitors, and metformin).
Combined administration of γ-secretase and COX-2 inhibitor produced a marked inhibition of growth in AGS cells, which suggests that patients with poorly differentiated GC may benefit from the blockage of NICD, which potentially serves a role in GC differentiation.
A pathway analysis of human gastric cancer shows that both the COX-2 pathway and Wnt/β-catenin signaling are significantly activated in tubular-type gastric cancer, and basal levels of these pathways are also increased in other types of gastric cancer.
Together, these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX-2 in H. pylori pathogenesis and may lead to new approaches for early detection and effective therapy of gastric cancer
COX-2 may play an important role in the development of gastric cancer, and the over-expression of COX-2 protein may be a high risk factor for liver metastasis.
In addition, our findings also suggest that reduction of COX-2 using nonsteroidal anti-inflammatory drugs in gastric cancer chemoprevention may only be relevant for older patients.
Immunohistochemical examination of surgical specimens showed a positive correlation among COX-2, vascular endothelial growth factor (VEGF), and vasculature in GC.
Cyclooxygenase-2 (COX-2) is overexpressed in and correlated with gastric cancer, and knockdown of COX-2 or administration of COX-2 inhibitors suppresses tumor formation in models of gastric cancer.