具核梭杆菌诱导缺氧诱导因子及血管生成因子高表达对食管鳞癌患者生存预后的影响

doi:10.6040/j.issn.1671-7554.0.2023.0655

摘要/Abstract

摘要： 目的分析食管鳞癌(ESCC)中具核梭杆菌(Fn)对缺氧诱导因子(HIF-1α)及血管生成因子(VEGF)的诱导效应,并探讨3个指标对ESCC患者生存预后的影响。方法将ESCC细胞(KYSE30和KYSE150)分为对照组和Fn感染组。采用Western blotting法、CCK8法及平板克隆法检测各组细胞的HIF-1α与VEGF表达量、紫杉醇(PTX)与顺铂(CDDP)应答效力及体外增殖能力。采用RNA scope法及免疫组化法检测309例ESCC组织中Fn感染、HIF-1α及VEGF的表达。采用Kaplan-Meier生存法分析比较Fn+HIF-1α+VEGF高风险组与低风险组生存时间差异。结果与对照组相比,Fn感染组细胞的HIF-1α与VEGF表达量、PTX与CDDP半数抑制浓度及体外增殖能力均增高(P<0.05)。ESCC组织中Fn感染率、HIF-1α及VEGF阳性率分别为43.04%、65.37%及60.52%,三者具有显著一致性(P<0.05)。与Fn+HIF-1α+VEGF低风险组相比,Fn+HIF-1α+VEGF高风险组术后5年生存时间显著缩短(P<0.05)。结论 Fn感染可诱导HIF-1α与VEGF高表达,降低ESCC细胞对化疗药物的敏感性,促进其恶性增殖,导致ESCC患者生存预后差。

关键词: 食管鳞癌, 具核梭杆菌, 缺氧诱导因子, 血管生成因子, 预后

Abstract: Objective To investigate the induction effect of Fusobacterium nucleatum(Fn)on hypoxia inducible factor-1(HIF-1α)and vascular endothelial growth factor(VEGF)in esophageal squamous cell carcinoma(ESCC), and to explore the influence of the above three indexes on the survival and prognosis of ESCC patients. Methods ESCC cells(KYSE30 and KYSE150)were divided into control and Fn infection groups. The expressions of HIF-1α and VEGF, the response efficacy of paclitaxel(PTX)and cisplatin(CDDP), and the in vitro proliferation ability of cells were detected with Western blotting, CCK8 and plate cloning, respectively. The Fn infection and expressions of HIF-1α and VEGF in 309 ESCC tissues were determined with RNA scope and immunohistochemistry. The difference in survival between Fn+HIF-1α+VEGF high-risk and low-risk groups were compared with Kaplan-Meier survival analysis. Results Compared with the control group, the Fn infection group had increased expressions of HIF-1α and VEGF, the 50% inhibitory concentration of PTX and CDDP, and the proliferation capacity(P<0.05). The Fn infection rate, HIF-1α and positive rate of VEGF in ESCC tissues were 43.04%, 65.37% and 60.52%, respectively, with significant consistency(P<0.05). Compared with Fn+HIF-1α+VEGF low-risk group, the high-risk group had significantly shortened 5-year survival(P<0.05). Conclusion Fn infection can induce the high expression of HIF-1α and VEGF, reduce the sensitivity of ESCC cells to chemotherapy drugs, promote their malignant proliferation, and lead to poor prognosis of ESCC patients.

Key words: Esophageal squamous cell carcinoma, Fusobacterium nucleatum, Hypoxia inducible factor-1, Vascular endothelial growth factor, Prognosis

中图分类号:

R735.1

华月帆,何珂瑶,张家豪,钱梦凡,刘怡文,孔金玉,杨海军,周福有. 具核梭杆菌诱导缺氧诱导因子及血管生成因子高表达对食管鳞癌患者生存预后的影响[J]. 山东大学学报 (医学版), 2023, 61(11): 59-67.

HUA Yuefan, HE Keyao, ZHANG Jiahao, QIAN Mengfan, LIU Yiwen, KONG Jinyu, YANG Haijun, ZHOU Fuyou. Effects of high expressions of hypoxia inducible factor-1 and vascular endothelial growth factor induced by Fusobacterium nucleatum on survival and prognosis of patients with esophageal squamous cell carcinoma[J]. Journal of Shandong University (Health Sciences), 2023, 61(11): 59-67.

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