南方医科大学学报2024，Vol.44Issue(5)：974-980,7.DOI:10.12122/j.issn.1673-4254.2024.05.20
胃癌组织中高表达ATP5A1与患者术后的不良预后和肿瘤细胞的糖代谢有关
High expression of ATP5A1 in gastric carcinoma is correlated with a poor prognosis and enhanced glucose metabolism in tumor cells
摘要
Abstract
Objective To analyze the expression level of ATP5A1 in gastric carcinoma and its influence on the prognosis of the patients and glucose metabolism in the tumor cells.Methods We retrospectively analyzed the data of 115 patients undergoing radical resection of gastric carcinoma in our hospital from February,2013 to November,2016.ATP5A1 expression in the surgical specimens were detected using immunohistochemistry,and the long-term prognosis of the patients with high(n=58)and low ATP5A1 expression(n=57)were analyzed.In gastric carcinoma MGC803 cells,the effects of lentivirus-mediated ATP5A1 knockdown or overexpression on glucose metabolism were investigated.We also observed the growth and glucose metabolism of xenografts derived from MGC803 cells with ATP5A1 knockdown or overexpression in nude mice.Results ATP5A1 was significantly overexpressed in gastric carcinoma tissues in close correlation with blood CEA and CA19-9 levels,pathological grade,T stage and N stage(P<0.05).ATP5A1 overexpression was an independent risk factor for a significantly lowered 5-year survival rate of patients with gastric carcinoma(P<0.05).ROC curve analysis demonstrated the predictive value of high ATP5A1 expression for the patients'prognosis(P<0.001).In MGC803 cells,ATP5A1 overexpression significantly up-regulated cellular glucose uptake and lactate production and increased the protein levels of HK2,PFK1,and LDHA(P<0.05),while ATP5A1 knockdown produced the opposite changes(P<0.05).In the tumor-bearing mice,overexpression of ATP5A1 increased glucose metabolism of the tumor cells and promoted tumor growth(P<0.05).Overexpression of ATP5A1 promoted the expressions of p-JNK and p-JUN in MGC803 cells(P<0.05),and the JNK inhibitor SP600125 significantly inhibited the enhancement of cellular glucose metabolism induced by ATP5A1 overexpression(P<0.05).Conclusion High ATP5A1 expression in gastric cancer is associated a poor long-term prognosis of the patients,and its effect is mediated at least partly by promoting glucose metabolism of the cells through the JNK/JUN pathway.关键词
ATP5A1/胃癌/糖代谢/预后/JNK/JUN通路Key words
ATP5A1/gastric carcinoma/glucose metabolism/prognosis/JNK/JUN pathway引用本文复制引用
杨晶晶,左芦根,殷丽霞,段婷,牛民主,何震东,陈心蕊,张小凤,李静,耿志军..胃癌组织中高表达ATP5A1与患者术后的不良预后和肿瘤细胞的糖代谢有关[J].南方医科大学学报,2024,44(5):974-980,7.基金项目
安徽省卫生健康科研项目(AHWJ2022a019) （AHWJ2022a019）
蚌埠医学院第一附属医院杰出青年基金(2019byyfyjq01) （2019byyfyjq01）
安徽省高校优秀青年人才支持计划重点项目(gxyqZD2022066) （gxyqZD2022066）
