PTEN/p16 inhibits inflammatory response and reduces intestinal metaplasia in gastric mucosa of chronic atrophic gastritis and prevents the carcinogenesis

Kailiang Chen^1#, Yu Liu^2#, Chaoqun Wang^3*, Jiafang Xu⁴*, Jian Gong⁵

¹Department of Ultrasound, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, China - ²Department of Breast and Thoracic Oncological Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, China - ³Department of Nuclear Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China - ⁴Reproductive Medicine Center, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, China - ⁵Department of Gastroenterology, Taian City Central Hospital, Taian 271000, China

Objective: To investigate the protective roles of phosphate and tension homology deleted on chromsome ten (PTEN)/p16 in gastric cancer (GC) progression by reducing the production of proinflammatory cytokines and intestinal metaplasia (IM) in gastric mucosa of chronic atrophic gastritis (CAG). 

Methods: Thirty normal persons (normal group), 30 CAG patients with small intestinal metaplasia (SIM) (CAG+SIM group), 30 CAG patients with colonic intestinal metaplasia (CIM) (CAG+CIM group), and 30 GC patients (GC group) were enrolled. The gastric mucosa tissues were collected. The expressions of PTEN, p16, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), caudal type homeobox transcription factor (CDX) 1 and CDX2 were detected. The correlations of these indexes in GC tissues were analyzed. Moreover, the expressions of PTEN and p16 in GC cell lines were detected. After over-expressed PTEN and p16 in GC cells were constructed successfully, the expression changes of IL-1β, TNF-α, CDX1 and CDX2 were measured, and the roles of PTEN and p16 in GC cell proliferation and tumor growth abilities were analyzed. 

Results: The expression levels of PTEN and p16 were decreased while IL-1β and TNF-α, CDX1 and CDX2 were increased in gastric mucosa in CAG+SIM, CAG+CIM and GC groups, compared with normal group. The degrees of these decreased and increased tendencies of above genes were associated with the degree of IM and canceration of gastric mucosa. The levels of IL-1β, TNF-α, CDX1 and CDX2 were negatively correlated with PTEN and p16 in GC specimens. Besides, PTEN and p16 expressions were declined in diverse GC cell lines, and the over-expression of PTEN and p16 could restrain the expressions of IL-1β, TNF-α, CDX1 and CDX2 as well as inhibit the GC cell proliferation and tumor growth.

Conclusion: PTEN and p16 can inhibit the inflammatory response and reduce the IM in gastric mucosa of CAG and prevent the occurrence of carcinogenesis.