探讨 RAGE 与其配体 HMGB1 之间的关系，以及糖尿病合并胃癌的预后和发病机制。

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

机构信息

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

出版信息

Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1339-1350. doi: 10.26355/eurrev_202102_24841.

DOI:10.26355/eurrev_202102_24841

PMID:33629304

Abstract

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.

摘要

目的

探讨晚期糖基化终产物受体（RAGE）和高迁移率族蛋白 B1（HMGB1）的表达与合并糖尿病的胃癌（GC）患者临床病理参数及预后的关系。

方法

收集 30 例正常胃黏膜组织、30 例 GC 组织、90 例 GC 合并 DM 组织及其临床资料，采用免疫组化法检测 RAGE 和 HMGB1 的表达水平，Kaplan-Meier 生存曲线分析 RAGE 和 HMGB1 的表达水平与 5 年生存率的关系，MTT 及细胞划痕实验检测敲低 RAGE 和 HMGB1 对 BGC-823 细胞增殖和迁移的影响，实时荧光定量 PCR 检测 RAGE 和 HMGB1 对聚嘧啶 tract 结合蛋白 1（PTBP-1）的调控，Spearman 相关性分析 RAGE 和 HMGB1 与 PTBP-1 的相关性。

结果

与正常胃黏膜组比较，GC 组、GC 合并 DM 组 RAGE 和 HMGB1 表达水平明显升高，RAGE 和 HMGB1 的表达与淋巴结转移、TNM 分期、肿瘤浸润有关（p<0.05）。年龄、TNM 分期、肿瘤浸润深度、RAGE 和 HMGB1 的表达与 GC 合并 DM 患者的预后有关（p<0.05）。肿瘤浸润深度、RAGE 和 HMGB1 的表达可影响 GC 合并 DM 患者的 5 年生存率（p<0.05）。

结论

敲低 RAGE 和 HMGB1 增加了 PTBP-1 的表达，RAGE 和 HMGB1 与 PTBP-1 呈负调控关系。RAGE 和 HMGB1 是 GC 合并 DM 患者预后的独立危险因素。RAGE 和 HMGB1 可能通过调控 PTBP-1 的表达抑制细胞糖酵解，进而影响 GC 细胞的增殖和迁移。