食管癌患者血清HIF-1α、HO-1、iNOS水平及其与氟尿嘧啶化疗敏感性的关系

Expressions of serum HIF-1α,HO-1 and iNOS in patients with esophageal cancer and their relationships with fluorouracil chemotherapy sensitivity

目的分析食管癌患者血清缺氧诱导因子-1α(HIF-1α)、血红素加氧酶-1(HO-1)、诱导型一氧化氮合酶(iNOS)水平及其与氟尿嘧啶化疗敏感性的关系。方法选取2018年4月至2021年7月西安医学院第一附属医院的初治食管癌患者102例为食管癌组,所有患者均采用氟尿嘧啶化疗。比较不同特征食管癌患者化疗前血清HIF-1α、HO-1、iNOS水平,比较不同特征食管癌患者的治疗效果。采用无序多分类Logistic回归分析影响食管癌患者化疗敏感性的因素;采用受试者工作特征(ROC)曲线分析血清HIF-1α、HO-1、iNOS水平对患者化疗敏感性的预测价值。结果食管癌患者血清HIF-1α、HO-1、iNOS水平分别为(192.75±49.93)ng/mL、(4.47±1.05)μg/L、(71.93±19.75)U/L。低分化、TNM分期为Ⅳ期、有淋巴结转移食管癌患者血清HIF-1α、HO-1、iNOS水平高于中、高分化,TNM分期为Ⅱ、Ⅲ期,无淋巴结转移患者,差异有统计学意义(P<0.05)。102例食管癌患者治疗有效率为78.43%,治疗无效率为21.57%。化疗有效患者化疗前及化疗后血清HIF-1α、HO-1水平均低于化疗无效患者,且化疗有效患者化疗前后差值大于化疗无效患者,差异有统计学意义(P<0.05);化疗有效患者化疗前血清iNOS水平高于化疗无效患者,化疗有效患者化疗前后差值大于化疗无效患者,差异有统计学意义(P<0.05)。化疗前血清HIF-1α、HO-1、iNOS联合检测预测氟尿嘧啶化疗疗效的曲线下面积(AUC)为0.859,明显高于3项指标单独检测的AUC(0.749、0.738、0.739,P<0.05)。结论食管癌患者血清HIF-1α、HO-1、iNOS高表达与TNM分期、病理分级、淋巴结转移关系密切,化疗前HIF-1α、HO-1低表达,iNOS高表达患者具有更强的氟尿嘧啶化疗敏感性。

Objective To investigate the serum levels of hypoxia-inducible factor-1α(HIF-1α),heme oxygenase-1(HO-1)and inducible nitric oxide synthase(iNOS)in patients with esophageal cancer and their relationships with chemotherapy sensitivity to fluorouracil.Methods From April 2018 to July 2021,102 patients with initially treated esophageal cancer in the First Affiliated Hospital of Xi'an Medical College were selected as the esophageal cancer group.All patients were treated with fluorouracil chemotherapy.The results of serum HIF-1α,HO-1 and iNOS levels before chemotherapy in patients with esophageal cancer with different characteristics were compared,and the therapeutic effect of patients with esophageal cancer with different characteristics was compared.Disordered multiple Logistic regression was used to analyze the factors affecting chemotherapy sensitivity of patients with esophageal cancer.The predictive value of serum HIF-1α,HO-1 and iNOS on chemotherapy sensitivity was analyzed by receiver operating characteristic(ROC)curve.Results The serum levels of HIF-1α,HO-1 and iNOS were(192.75±49.93)ng/mL,(4.47±1.05)μg/L and(71.93±19.75)U/L respectively.The levels of HIF-1α,HO-1 and iNOS in patients with low differentiation,TNM stageⅣand lymph node metastasis were higher than those in patients with middle and high differentiation,TNM stageⅡandⅢ,no lymph node metastasis,the differences were statistically significant(P<0.05).The effective rate of 102 patients with esophageal cancer was 78.43%,and the ineffective rate was 21.57%.Serum HIF-1αand HO-1 levels in patients with effective chemotherapy before and after chemotherapy were lower than those in patients with ineffective chemotherapy,the differences before and after chemotherapy in patients with effec-tive chemotherapy were greater than those in patients with ineffective chemotherapy,the differences were sta-tistically significant(P<0.05).The levels of iNOS in serum in patients with effective chemotherapy before chemotherapy was higher than that in patients with ineffective chemotherapy,the difference before and after chemotherapy in patients with effective chemotherapy was greater than that in patients with ineffective chem-otherapy,with statistical significance(P<0.05).The area under the curve(AUC)of the combined detection of HIF-1α,HO-1 and iNOS before chemotherapy to predict the chemotherapy efficacy of fluorouracil was 0.859,which was significantly higher than that of the AUC detected by the three indicators alone(0.749,0.738,0.739,P<0.05).Conclusion The high expression of HIF-1α,HO-1 and iNOS in serum of patients with esophageal cancer relate closely to tumor stage,differentiation degree and lymph node metastasis.Pa-tients with low expression of HIF-1αand HO-1 and high expression of iNOS before chemotherapy have stron-ger sensitivity to fluorouracil chemotherapy.