首页|具核梭杆菌对食管鳞状细胞癌铁死亡相关蛋白表达及预后的影响

具核梭杆菌对食管鳞状细胞癌铁死亡相关蛋白表达及预后的影响

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目的:探讨具核梭杆菌(Fn)对食管鳞状细胞癌(ESCC)铁死亡相关蛋白缺氧诱导因子-1α(HIF-1α)及谷胱甘肽过氧化物酶4(GPX4)表达及预后的影响.方法:将ESCC细胞KYSE30及KYSE150各分为4组:对照组(不感染Fn),Fn感染12、24、48 h组.采用试剂盒检测细胞中活性氧(ROS)与丙二醛(MDA)含量,CCK8法检测顺铂(CDDP)对KYSE30和KYSE150细胞的半数抑制浓度(IC50),Western blot法检测HIF-1α与GPX4蛋白表达水平.采用RNAscope技术检测222例ESCC及其癌旁正常食管组织中Fn感染情况,采用免疫组化法检测HIF-1α与GPX4蛋白的表达情况.采用Kaplan-Meier法绘制Fn感染阳性和阴性ESCC患者术后生存曲线.结果:Fn感染可诱导KYSE30及KYSE150细胞HIF-1α和GPX4蛋白高表达,提高细胞的氧化应激水平,并降低细胞对CDDP的应答效力,具有时间依赖性(P＜0.05).ESCC组织中Fn感染,HIF-1α及GPX4蛋白表达的阳性率均高于癌旁正常食管组织(P＜0.05).ESCC患者中男性、有吸烟史、有饮酒史、肿瘤低分化、肿瘤浸润深度侵及纤维膜、有淋巴结转移、TNM分期Ⅲ/Ⅳ期者Fn感染阳性率增加(P＜0.05).Fn感染阳性的ESCC患者术后生存状况较Fn感染阴性者差(P＜0.001).结论:Fn感染可抑制ESCC铁死亡,可能与ESCC患者预后不良有关.
Effect of Fusobacterium nucleatum regulating ferroptosis related protein expression on prognosis of esophageal squamous cell carcinoma
Aim:To investigate the effect of Fusobacterium nucleatum(Fn)on the expressions of ferroptosis related protein hypoxia-inducible factor-1α(HIF-1α)and glutathione peroxidase 4(GPX4)in esophageal squamous cell carcinoma(ESCC)and prognosis of ESCC patients.Methods:ESCC KYSE30 and KYSE150 cells were allocated into 4 groups:control group,Fn infection group for 12 hours group,Fn infection group for 24 hours group and Fn infection group for 48 hours group.ROS and MDA kits were used to detect the content of oxidative stress indexes in cells.IC50 of cisplatin(CDDP)on KYSE30 and KYSE150 cells was detected by CCK8 kit,and the expression levels of HIF-1α and GPX4 were detected by Western blot.Fn infection in 222 cases of ESCC and adjacent normal esophageal tissues were detected by RNAscope tech-nique,and the expression of HIF-1α and GPX4 was detected by immunohistochemistry.Kaplan-Meier method was used to draw survival curves of ESCC patients with positive or negative Fn infection.Results:Fn infection induced the high expres-sions of HIF-1α and GPX4 protein in KYSE30 and KYSE150 cells,enhanced the level of oxidative stress,and decreased the response to CDDP in a time-dependent manner(P＜0.05).The positive rates of Fn infection,HIF-1α and GPX4 protein ex-pression in ESCC tissue were higher than those in adjacent normal esophageal tissue(P＜0.05).In ESCC patients,the posi-tive rate of Fn infection was increased in males,and patients with smoking history,drinking history,low tumor differentia-tion,tumor invasion depth in fibrous membrane,lymph node metastasis,TNM stage Ⅲ/Ⅳ(P＜0.05).The survival of ESCC patients with Fn infection was worse than that without Fn infection after operation(P＜0.001).Conclusions:Fn infection can induce ferroptosis of ESCC,which may be associated with poor prognosis of ESCC patients.

esophageal squamous cell carcinomaFusobacterium nucleatumHIF-1αGPX4prognosisferroptosis

龙情柔、周福有、张家豪、何珂瑶、张哲源、刘怡文、孔金玉、孙蔚、李军扩、代宁涛、杨海军

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河南科技大学临床医学院

河南科技大学第一附属医院 河南洛阳 471003

安阳市肿瘤医院胸外科 河南安阳 455000

河南省食管癌精准防治医学重点实验室 河南安阳 455000

新乡医学院第三附属医院胸外科 河南新乡 453003

安阳市肿瘤医院病理科 河南安阳 455000

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食管鳞状细胞癌 具核梭杆菌 HIF-1α GPX4 预后 铁死亡

河南省医学科技攻关省部共建青年项目河南省医学科技攻关省部共建青年项目安阳市重大科技专项安阳市重大科技专项河南科技大学第一附属医院科技攻关项目河南科技大学第一附属医院科技攻关项目

SBCJ202103099SBGJ202103100ZDKJJH20200062022A02SF002ZLKFJJ20230504ZLKFJJ20230513

2024

10.13705/j.issn.1671-6825.2023.04.037

郑州大学学报(医学版)
郑州大学

郑州大学学报(医学版)

CSTPCD北大核心
影响因子：1.246
ISSN：1671-6825
年,卷(期)：2024.59(4)
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