Research on the relationship between RAGE and its ligand HMGB1, and prognosis and pathogenesis of gastric cancer with diabetes mellitus

Y. Zhou, S.-X. Liu, Y.-N. Zhou, J. Wang, R. Ji

Department of Geriatrics (II), The First Hospital of Lanzhou University, Lanzhou, P.R. China. zhouyun467@163.com

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• Oncology

OBJECTIVE: To investigate the relationship between the expression of receptor for advanced glycation end products (RAGE) and high-mobility group box-1 (HMGB1) and the clinical and pathological parameters and prognosis of the patients with gastric cancer (GC) with diabetes mellitus (DM).

PATIENTS AND METHODS: 30 normal gastric mucosa, 30 tissues with GC, 90 tissues with GC and DM and their clinical data were collected. The expression levels of RAGE and HMGB1 were detected by immunohistochemistry. Kaplan-Meier survival curve was used to analyze the relationship between the expression levels of RAGE and HMGB1 and the 5-year survival rate. MTT and cell scratch assays were used to detect the effects of knockdown RAGE and HMGB1 on the proliferation and migration of BGC-823 cells. Real-Time PCR was used to detect the regulation of RAGE and HMGB1 on PTBP-1, and Spearman correlation analysis was performed to analyze the correlation between RAGE and HMGB1 and Polyprimidine tract protein (PTBP-1).

RESULTS: Compared with the normal gastric mucosa group, the expression levels of RAGE and HMGB1 were significantly higher in the GC group, GC with DM group. The expression of RAGE and HMGB1 was related with lymph node metastasis, TNM staging, and tumor invasion (p<0.05). Age, TNM stage, tumor infiltration depth, the expression of RAGE and HMGB1 were related with prognosis of patients with GC and DM (p<0.05). Tumor infiltration depth, the expression of RAGE and HMGB1 could affect the 5-year survival rate of patients with GC and DM (p<0.05).

CONCLUSIONS: Knockdown RAGE and HMGB1 increased the expression of PTBP-1, and RAGE and HMGB1 were negatively regulated with PTBP-1. RAGE and HMGB1 are independent risk factors for the prognosis of patients with GC with DM. RAGE and HMGB1 may regulate the expression of PTBP-1 and inhibit the glycolysis of cells, which may affect the cell proliferation and migration of GC.

 

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