铁死亡相关基因TFRC在胃癌组织中的表达及其与化疗药物敏感性的关系

Expression of iron death related gene TFRC in gastric cancer tissue and its relationship with chemotherapy drug sensitivity

目的:探讨转铁蛋白受体(TFRC)在胃癌组织中的表达及其与化疗药物敏感性的关系。方法:选取2018年4月至2020年4月医院胃肠外科收治接受胃癌切除术治疗的胃癌患者112例,并收集手术切除的新鲜胃癌组织及距肿瘤边缘>5 cm的癌旁组织。制备组织石蜡切片,分别采用免疫组织化学SP染色和原位杂交染色检测组织中TFRC蛋白及mRNA表达。制备胃癌组织单细胞悬液,采用MTT比色法分析TFRC表达与化疗药物敏感性的关系。术后随访3年,绘制Kaplan-Meier生存曲线,分析TFRC表达与胃癌患者预后的关系。结果:胃癌组织中TFRC蛋白阳性表达率为67.86%,高于癌旁组织中的21.43%,差异具有统计学意义(P<0.05)。胃癌组织中TFRC mRNA阳性表达率为60.71%,高于癌旁组织中的15.18%,差异具有统计学意义(P<0.05)。胃癌组织中TFRC蛋白与mRNA表达呈显著正相关(P<0.05)。肿瘤最大直径≥5 cm、临床分期Ⅲ-Ⅳ期、低分化、浸润深度T_(3)+T_(4)期、有淋巴结转移的胃癌患者TFRC蛋白和mRNA阳性表达率更高,差异具有统计学意义(P<0.05)。胃癌组织中TFRC蛋白和mRNA阴性表达患者顺铂(DDP)、环磷酰胺(CTX)、氟尿嘧啶(5-FU)、氨甲蝶呤(MTX)敏感性高于阳性表达者,差异具有统计学意义(P<0.05)。化疗敏感组患者胃癌组织中TFRC蛋白和mRNA阳性率低于化疗耐药组,差异具有统计学意义(P<0.05)。胃癌组织中TFRC表达是胃癌患者化疗敏感性的独立危险因素(P<0.05)。胃癌组织中TFRC蛋白和mRNA阳性表达的患者无病生存期(DFS)率及总生存期(OS)率均低于阴性表达者,差异具有统计学意义(P<0.05)。结论:TFRC在胃癌组织中呈阳性表达,可能参与胃癌发生及发展,并与患者预后密切相关,且TFRC细胞表达增高时,对化疗药物敏感性亦增加,可作为胃癌术后辅助化疗效果的预测指标,为治疗提供参考。

Objective:To investigate the expression of transferrin receptor(TFRC) in gastric cancer tissue and its relationship with chemotherapy drug sensitivity.Methods:A total of 112 gastric cancer patients admitted to the gastrointestinal surgery department of the hospital from April 2018 to April 2020 who underwent gastric cancer resection were selected,and fresh gastric cancer tissues and adjacent tissues greater than 5 cm from the tumor edge were collected.Prepare tissue paraffin sections and detect the expression of TFRC protein and mRNA in tissues using immunohistochemistry SP staining and in situ hybridization staining,respectively.Prepare a single cell suspension of gastric cancer tissue and analyze the relationship between TFRC expression and chemotherapy drug sensitivity using MTT colorimetry.Follow up for 3 years after surgery,draw Kaplan-Meier survival curve,and analyze the relationship between TFRC expression and prognosis of gastric cancer patients.Results:The positive expression rate of TFRC protein in gastric cancer tissue was 67.86%,which was higher than 21.43% in adjacent tissue,and the difference was statistically significant(P<0.05).The positive expression rate of TFRC mRNA in gastric cancer tissue was 60.71%,which was higher than 15.18% in adjacent tissue,and the difference was statistically significant(P<0.05).There was a significant positive correlation between TFRC protein and mRNA expression in gastric cancer tissue(P<0.05).The positive expression rates of TFRC protein and mRNA were higher in gastric cancer patients with tumor maximum diameter ≥5 cm,clinical stage Ⅲ-Ⅳ,poor differentiation,invasion depth T_(3)+T_(4) stage and lymph node metastasis,and the difference was statistically significant(P<0.05).Patients with negative expression of TFRC protein and mRNA in gastric cancer tissue showed higher sensitivity to cisplatin(DDP),cyclophosphamide(CTX),fluorouracil(5-FU),and methotrexate(MTX) compared to those with positive expression,and the difference was statistically significant(P<0.05).The positive rate of TFRC protein and mRNA in gastric cancer tissue of chemotherapy-sensitive group was lower than that of chemotherapy-resistant group,and the difference was statistically significant(P<0.05).The expression of TFRC in gastric cancer tissue was an independent risk factor for chemotherapy sensitivity of gastric cancer patients(P<0.05).The disease-free survival(DFS) rate and overall survival(OS) rate of patients with positive expression of TFRC protein and mRNA in gastric cancer tissue were lower than those with negative expression,and the difference was statistically significant(P<0.05).Conclusion:TFRC is positively expressed in gastric cancer tissue,which may be involved in the occurrence and development of gastric cancer,and is closely related to the prognosis of patients.When the expression of TFRC cells increases,the sensitivity to chemotherapy drugs also increases,which can be used as a predictor of the effect of postoperative adjuvant chemotherapy for gastric cancer and provide reference for treatment.