高原地区胃癌病人组织低氧诱导因子表达与临床特征及预后相关性研究

Study on the relationship between the expression of hypoxia inducible factors and clinical features and prognosis in patients with gastric cancer in plateau area

目的探讨高原地区胃癌病人组织低氧诱导因子(HIF)的表达与临床特征及预后相关性。方法随机选取2015年9月~2017年7月在我院进行胃癌根治术的病人62例,采用免疫组织化学染色方法检测胃癌组织和癌旁组织HIF-1α蛋白的表达,对免疫组织化结果和临床特征进行相关性分析,采用高效液相色谱法同时检测HIF-1α的DNA甲基化水平,分析HIF-1α蛋白的表达和DNA甲基化表达的相关性,采用Kaplan-Meier法分析HIF-1α的表达对术后病人生存时间的影响。结果在所收集的62例胃癌组织和癌旁组织中,有44例(70.97%)胃癌组织中HIF-1α表达上调,正常组织与癌组织的表达量分别为(4.80±0.29)和(3.09±0.09),两组间比较差异有统计学意义(P<0.05),与肿瘤直径和胃癌不同的发病部位以及TNM分期有显著相关(P<0.05)。HIF-1α表达率越高,肿瘤越大,并且HIF-1α在胃体部肿瘤的高表达率要显著高于胃窦和贲门。DNA甲基化比较,正常组织与癌组织水平分别为(0.158±0.010)和(0.362±0.009),两组间比较差异有统计学意义(P<0.05)。HIF-1α低表达组的总生存率(HR=0.601,P=0.002)和无复发生存率(HR=0.498,P=0.003)均高于HIF-1α高表达组。结论 HIF-1α高表达于胃癌组织中,推测出可能会加速胃癌的分化表达和转移,同时可以作为判定病人预后的参考。

Objective To explore the relationship between the expression of hypoxia-inducible factors and clinical features and prognosis of patients with gastric cancer in plateau areas.Methods 62 cases of patients who underwent radical gastric cancer surgery in our hospital from September 2015 to July 2017 were randomly selected.Immunohistochemical staining methods were used to detect the expression of HIF-1α protein in gastric cancer tissues and adjacent tissues.Correlation analysis between chemical results and clinical features, using high performance liquid chromatography to detect HIF-1α DNA methylation level, and then analyzing the correlation between HIF-1αproteinand DNA methylation expression, and then using Kaplan-Meier Method to analyze the effect of HIF-1α proteinexpression on the survival time of patients after surgery.Results Among the 62 cases of gastric adenocarcinoma and adjacent parts collected, 44 cases(70.97%) of gastric cancer parts had up-regulated HIF-1α factor manifestation levels.The manifestation levels of normal parts and cancer parts were(4.80±0.29) and(3.09±0.09),respectively.There was a imparity between the two(P<0.05).Statistics of immunohistochemical results showed that the expression level of HIF-1α proteinin gastric cancer tissue was not significantly related to the patient’s age and gender(P<0.05).The higher the expression rate of HIF-1αmRNA,the larger the tumor, and the high expression rate of HIF-1α proteinin gastric body tumors is significantly higher than that of gastric antrum and cardia.Comparing DNA methylation, the expression levels of normal and cancer tissues were(0.158±0.010) and(0.362±0.009),respectively.There was a imparity between the two(t=6.806,P<0.001).The rate of survivors(HR=0.601,P=0.002) and recurrence-free rate of survivors(HR=0.498,P=0.003) of the HIF-1α low manifestation group were dramaticlly higher than these in the HIF-1α high manifestation group.Conclusion HIF-1α is highly expressed in gastric cancer tissues.It is speculated that it may accelerate the differentiation, expression and metastasis of gastric cancer, and can be used as a reference for determining the prognosis of patients.