目的:探索磷酸果糖激酶血小板型(platelet-type phosphofructokinase,PFKP)在肺腺癌(adenocarcinoma of lung,LUAD)中的关键作用。方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库观察PFKP在肺腺癌组织和癌旁组织中的表...目的:探索磷酸果糖激酶血小板型(platelet-type phosphofructokinase,PFKP)在肺腺癌(adenocarcinoma of lung,LUAD)中的关键作用。方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库观察PFKP在肺腺癌组织和癌旁组织中的表达情况。采用免疫组化检测临床样本肺腺癌组织和癌旁组织PFKP表达情况。利用TCGA数据库进一步探讨PFKP的表达及其在LUAD预后和免疫浸润中的作用。结果:PFKP在LUAD中高表达,且PFKP高表达与临床病理特征(AJCC分期和TNM分期)及不良预后相关。Kaplan-Meier生存分析和ROC曲线分析进一步证实,PFKP高表达组患者的中位总生存时间显著低于低表达组,且在1年、3年和5年生存预测中呈现出高度预测性。富集分析表明,PFKP的生物学功能参与到抗肿瘤药物代谢的过程中。此外PFKP与肿瘤微环境和免疫治疗密切相关。本研究筛选出一批对PFKP高表达的LUAD患者敏感性较高的临床药物和正在被研究的抑制剂。结论:PFKP在LUAD发生发展中的关键作用和其作为潜在药物治疗靶标的可能性,使其成为肺癌研究和治疗的重要靶标。展开更多
Aim:Cancer-related deaths are primarily caused by lung cancer around the world.The prognosis and burden of lung cancer must be improved by identifying novel biomarkers for diagnosis and treatment.In non-small cell lun...Aim:Cancer-related deaths are primarily caused by lung cancer around the world.The prognosis and burden of lung cancer must be improved by identifying novel biomarkers for diagnosis and treatment.In non-small cell lung cancer(NSCLC),the platelet isoform of phosphofructokinase 1(PFKP)has been identified as a tumor-promoting oncogene.The current study examined the specific role that PFKP plays in NSCLC tumorigenesis,as well as the underlying mechanism.Methods:A lung cancer dataset was obtained from the TCGA in order to examine the expression of PFKP.Using the Kaplan-Meier Plotter website,we calculated the overall survival(OS)along with the recurrence-free survivals(RFS)curves with high and low levels of PFKP in lung cancer.The mechanism by which zinc finger protein 148(ZNF148)regulated PFKP/PD-L1 levels in NSCLC was investigated through chromatin immunoprecipitation(ChIP),qRT-PCR,and western blotting.In order to uncover ZNF148's function in NSCLC,subsequent functional studies included CCK-8,colony formation,and Transwell,along with glycolysis assays.Student’s T-test was conducted for data analysis with GraphPad Prism 9.0.Results:The expression of PFKP in NSCLC was increased,and it was linked to worse outcomes.This increased expression of PFKP in NSCLC was induced by ZNF148.Silencing ZNF148 remarkably dampened NSCLC cell proliferation,invasion,and glycolysis capacities.According to a mechanistic study,ZNF148 regulates the PFKP/PD-L1 axis,which promotes NSCLC tumorigenesis.Conclusion:It has been established that ZNF148-induced PFKP is key to the proliferation,invasion,and glycolysis abilities of NSCLC cells by regulating PD-L1 expression.Therefore,the ZNF148/PFKP/PD-L1 axis could be a potential biological signature and target for NSCLC diagnosis and treatment.展开更多
文摘目的:探索磷酸果糖激酶血小板型(platelet-type phosphofructokinase,PFKP)在肺腺癌(adenocarcinoma of lung,LUAD)中的关键作用。方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库观察PFKP在肺腺癌组织和癌旁组织中的表达情况。采用免疫组化检测临床样本肺腺癌组织和癌旁组织PFKP表达情况。利用TCGA数据库进一步探讨PFKP的表达及其在LUAD预后和免疫浸润中的作用。结果:PFKP在LUAD中高表达,且PFKP高表达与临床病理特征(AJCC分期和TNM分期)及不良预后相关。Kaplan-Meier生存分析和ROC曲线分析进一步证实,PFKP高表达组患者的中位总生存时间显著低于低表达组,且在1年、3年和5年生存预测中呈现出高度预测性。富集分析表明,PFKP的生物学功能参与到抗肿瘤药物代谢的过程中。此外PFKP与肿瘤微环境和免疫治疗密切相关。本研究筛选出一批对PFKP高表达的LUAD患者敏感性较高的临床药物和正在被研究的抑制剂。结论:PFKP在LUAD发生发展中的关键作用和其作为潜在药物治疗靶标的可能性,使其成为肺癌研究和治疗的重要靶标。
基金The Natural Science Foundation of Hunan Province(Nos.2021JJ40919)funded this study.
文摘Aim:Cancer-related deaths are primarily caused by lung cancer around the world.The prognosis and burden of lung cancer must be improved by identifying novel biomarkers for diagnosis and treatment.In non-small cell lung cancer(NSCLC),the platelet isoform of phosphofructokinase 1(PFKP)has been identified as a tumor-promoting oncogene.The current study examined the specific role that PFKP plays in NSCLC tumorigenesis,as well as the underlying mechanism.Methods:A lung cancer dataset was obtained from the TCGA in order to examine the expression of PFKP.Using the Kaplan-Meier Plotter website,we calculated the overall survival(OS)along with the recurrence-free survivals(RFS)curves with high and low levels of PFKP in lung cancer.The mechanism by which zinc finger protein 148(ZNF148)regulated PFKP/PD-L1 levels in NSCLC was investigated through chromatin immunoprecipitation(ChIP),qRT-PCR,and western blotting.In order to uncover ZNF148's function in NSCLC,subsequent functional studies included CCK-8,colony formation,and Transwell,along with glycolysis assays.Student’s T-test was conducted for data analysis with GraphPad Prism 9.0.Results:The expression of PFKP in NSCLC was increased,and it was linked to worse outcomes.This increased expression of PFKP in NSCLC was induced by ZNF148.Silencing ZNF148 remarkably dampened NSCLC cell proliferation,invasion,and glycolysis capacities.According to a mechanistic study,ZNF148 regulates the PFKP/PD-L1 axis,which promotes NSCLC tumorigenesis.Conclusion:It has been established that ZNF148-induced PFKP is key to the proliferation,invasion,and glycolysis abilities of NSCLC cells by regulating PD-L1 expression.Therefore,the ZNF148/PFKP/PD-L1 axis could be a potential biological signature and target for NSCLC diagnosis and treatment.
