幽门螺杆菌定植和铁死亡基因表达与胃癌临床病理及预后的关系

Association between Helicobacter Pylori Colonization and Iron Death Gene Expression and Clinicopathology and Prognosis of Gastric Cancer

目的探讨幽门螺杆菌定植与铁死亡基因表达与胃癌临床病理及预后的关系。方法选取159例于2018年1月至2019年9月在空军军医大学第一附属医院肿瘤防治中心接受D2胃癌根治术的胃癌患者。收集患者年龄、性别、术前常规实验室测量、术后肿瘤特征和生存期等资料。采用免疫组织化学分析癌旁正常组织和胃癌组织中溶质载体家族1成员5(SLC1A5)表达,采用酶联免疫吸附试验评估术前血清幽门螺杆菌免疫球蛋白G(IgG)抗体水平。结果有无幽门螺杆菌感染患者在T分期、淋巴结转移数量≥3和SLC1A5表达水平方面差异有统计学意义(P<0.05)。与癌旁正常组织相比,胃癌组织中SLC1A5免疫组织化学评分显著增加(6.35±3.40 vs 3.08±1.75,t=10.75,P<0.001)。SLC1A5低表达和高表达患者在肿瘤等级、神经侵犯、T分期、幽门螺杆菌感染方面差异有统计学意义(P<0.05)。Cox分析显示,幽门螺杆菌感染(HR=3.786、95%CI=2.284~6.274)、肿瘤等级(HR=1.877、95%CI=1.254~2.810)、SLC1A5表达(HR=1.112、95%CI=1.035~1.193)是胃癌患者预后不良的独立影响因素(P<0.05)。将幽门螺杆菌感染、肿瘤等级、SLC1A5表达三者组合,构建HSG评分,HSG 0分、HSG 1分、HSG 2分、HSG 3分死亡事件的发生率依次为6.25%(1/16)、34.29%(12/35)、64.91%(37/57)、88.23%(45/51),不同评分之间的总体生存概率比较差异有统计学意义(Log-rank=31.06,P<0.001)。结论幽门螺杆菌感染、肿瘤等级、SLC1A5表达是胃癌患者不良预后的独立影响因素,基于三者组合构建的HSG评分能有效地对胃癌根治性切除后患者的结局进行分层,并有助于改善临床决策和确定适当的治疗。

Objective To investigate the relationship between helicobacter pylori colonization,iron death gene expression and clinicopathological features and prognosis of gastric cancer.Methods 159 gastric cancer patients who underwent radical surgery for D2 gastric cancer at the Cancer Prevention and Control Center of the First Affiliated Hospital of Air Force Military Medical University from January 2018 to September 2019 were selected.Data on patients’age,gender,preoperative routine laboratory measurements,postoperative tumor characteristics and survival were collected.Immunohistochemistry was used to analyze the expression of solute carrier family 1 member 5(SLC1A5)in paracancerous normal tissues and gastric cancer tissues,and enzyme-linked immunosorbent assay was used to assess the preoperative serum level of helicobacter pylori immunoglobulin G(IgG)antibody.Results The difference between patients with and without H.pylori infection was statistically significant in terms of T stage,number of lymph node metastases≥3 and SLC1A5 expression level(P<0.05).SLC1A5 immunohistochemical scores were significantly increased in gastric cancer tissues compared with normal tissues adjacent to the cancer(6.35±3.40 vs 3.08±1.75,t=10.75,P<0.001).The difference between patients with low and high expression of SLC1A5 was statistically significant n tumor grade,nerve invasion,T stage and H.pylori infection(P<0.05).Cox analysis showed that H.pylori infection(HR=3.786,95%CI=2.284-6.274),tumor grade(HR=1.877,95%CI=1.254-2.810),SLC1A5 expression(HR=1.112,95%CI=1.035-1.193)were independent influencing factors of poor prognosis in patients with gastric cancer(P<0.05).The HSG score was constructed by combining H.pylori infection,tumor grade,and SLC1A5 expression,and the incidence of HSG 0,HSG 1,HSG 2,and HSG 3 fatal events was 6.25%(1/16),34.29%(12/35),64.91%(37/57),and 88.23%(45/51),respectively.The difference in overall survival probability comparison among different HSG scores was statistically significant(Log-rank=31.06,P<0.001).Conclusion Helicobacter pylori infection,tumor grade and SLC1A5 expression are independent influencing factors of poor prognosis in patients with gastric cancer.The HSG score based on the combination of the three factors can effectively stratify the outcomes of patients after radical resection,and help to improve clinical decision-making and ensure appropriate treatment.