Potential roles for PA28β in gastric adenocarcinoma development and diagnosis

Purpose This study aimed to investigate the expression level of human proteasome activator PA28β subunit (PA28β) in gastric adenocarcinomas (GA) tissues and investigate its potential role in GA carcinogenesis. Methods To investigate the expression profile of PA28β in patients with GA, we employed immunohistochemistry for detection of 287 cases of paired GA and adjacent non-neoplastic tissues. To evaluate the role of PA28β in GA cells, we measured cell growth, colony formation, soft agar, and nude mice tumorigenicity assays in MKN-45 GA cells pre- and post-PA28β transfection. Results PA28β had lower expression in 183 of 287 GA cases compared to paired normal samples (63.76%; P ≤ 0.001). Decreased expression was dependent on histological type, TNM stage, and differentiation grade. Significantly decreased expression was correlated with a diffuse histological type (88/116, 75.86%) compared to an intestinal type (84/152, 55.26%; P ≤ 0.001), with advanced TNM stages (T3: 44/59, 74.58%; T4:25/32, 78.13%) compared to earlier stages (T1: 25/47, 53.19%; T2: 90/149, 60.40%; P = 0.004), and poorer differentiation grade (poor: 68/90, 75.56%) compared to a higher grade (high: 9/18, 50%, moderate: 74/134, 55.22%) ( P = 0.006). Over-expression of PA28β inhibited cell growth, proliferation, and tumorigenicity of MKN-45 GA cells. Conclusions These results indicated that PA28β might participate in the origin and progression of GA cancer through changes to cell proliferation activity and tumorigenicity. Therefore, PA28β might be a novel biomarker for GA.