Abstract: Objective To investigate the effect of COX6B2 expression in gastric cancer tissues on the patients' long-term prognosis and its underlying mechanism. Methods Based on the public databases and the medical records of patients, we analyzed the expression level of COX6B2 in gastric cancer and adjacent tissues and its influence on long-term prognosis of the patients. Enrichment analysis were used to predict the possible role of COX6B2 in gastric cancer. The effects of lentivirus-mediated COX6B2 knockdown on biological behaviors of gastric cancer cells were examined using CCK-8 assay, flow cytometry, and Western blotting. Results TCGA database and the results of immunohistochemistry, Western blotting and real-time PCR all demonstrated a significantly higher expression of COX6B2 in gastric cancer tissues (P<0.05). Kaplan-Meier plotter database and Kaplan-Meier curves showed that the patients with high COX6B2 expression had significantly shorter postoperative survival (P<0.05). A high expression of COX6B2 in gastric cancer tissues was closely correlated with clinicopathologic stage, CEA and CA19-9 (P<0.05). A high expression of COX6B2, CEA level≥5 μg/L and CA19-9 level≥37 kU/L were independent risk factors affecting postoperative 5-year survival rate of gastric cancer patients (P<0.05), and COX6B2 expression level had a predictive value for long- term prognosis of the patients (P<0.05). GO and KEGG enrichment analyses showed that COX6B2 was mainly involved in the regulation of cell cycle. In the in vitro cell experiment, COX6B2 overexpression significantly promoted gastric cancer cell proliferation, increased the percentage of G1/S phase cells and inhibited the cellular expressions of p53 and p21 (P<0.05). Conclusions COX6B2 is highly expressed in gastric cancer and is closely correlated with a poor long-term prognosis of the patients possibly by promoting gastric cancer cell proliferation and regulating cell cycle.

Key words: gastric cancer; COX6B2; cell cycle; cell proliferation; long-term prognosis; p53