缺氧诱导因子1α 与甘氨酸甲基转移酶在胃癌组织中的表达及其临床意义

Effect of HIF- 1α and glycine methyltransferase on prognosis of gastric cancer

摘要:

目的 研究胃癌组与癌旁正常组织中缺氧诱导因子1α（HIF-1α）和甘氨酸甲基转移酶（GNMT）的表达及与病患预后的关系。方法 选取2015 年6 月-2016 年6 月于新疆医科大学附属肿瘤医院胃肠外科收治的胃癌患者45 例为研究对象。分别采集患者胃癌组织和癌旁正常组织标本，对比HIF-1α 和GNMT 在胃癌组织和癌旁正常组织的表达并分析其与患者预后的关系。结果 HIF-1α 在胃癌组织和癌旁组织中的表达率分别为84.44% 和4.45%，差异有统计学意义（P <0.05）；HIF-1α 在胃癌细胞胞核的阳性率高于胞质（64.44% vs 4.45%）（P <0.05）。GNMT 在胃癌组织和癌旁组织中的表达量分别为（678.23±221.88）和（1 136.73±332.81）ng/ml，差异有统计学意义（P <0.05）。多因素Cox 回归分析显示，影响胃癌患者5 年生存结局的独立因素包括HIF-1α 蛋白(+) 表达（P =0.002）、GNMT 蛋白（-）表达（P =0.006）、分化程度（P =0.036）、浸润深度（P =0.001）和远处转移（P =0.002）。结论 HIF-1α 在胃癌组织中高表达，而GNMT 在胃癌组织中低表达，并且与胃癌的预后有一定的联系，可作为判断胃癌患者预后的指标。

Abstract:

Objective To investigate the expression levels of hypoxia inducible factor-1α (HIF-1α) and glycine methyltransferase (GNMT) in patients with gastric cancer and potential association with prognosis. Methods Totally 45 cases of gastric cancer patients admitted to our hospital from June 2015 to June 2016 were included in this study.Cancer tissues and adjacent normal tissues were collected for further purposes. Expression of HIF-1α and GNMT were determined by Immunostaining method. Potential association between expression of target proteins and clinical outcome was analyzed. Results The positive rate of HIF-1α in gastric carcinoma was increased significantly compared with normal tissue (84.44% vs 4.45%, P < 0.05). Among HIF-1α expressing cells, nucleus positive rate was dramatically higher compared with cytoplasm positive rate (64.44% vs 4.45%, P < 0.05). Concentration of GNMT in gastric cancer tissue was downregulated when compared with that in normal tissue [(678.23 ± 221.88) ng/ml vs (1,136.73 ± 332.81) ng/ml, P < 0.05]. Multivariate Cox regression analysis showed that the independent factors for 5 year survival of patients included HIF-1 α protein (+) (P = 0.002), GNMT protein (-) (P = 0.006), differentiation degree (P = 0.036), invasion depth (P = 0.001), and distant metastasis (P = 0.002). Conclusion Expression of HIF-1α increases while GNMT decreases in gastric cancer tissue, which may be the prognostic factors for outcome of gastric tumor.