摘要
目的:探讨Neogenin在非小细胞肺癌(NSCLC)组织中的表达及患者预后中的临床价值,及其参与NSCLC发生发展的机制。方法:利用癌症基因组图谱(TCGA)的测序数据评估NSCLC中Neogenin表达水平与癌旁正常组织是否有差异;KM-plotter数据库的资料预测Neogenin在NSCLC及其不同组织亚型中的预后作用;进一步利用真实世界NSCLC的临床病理资料验证Neogenin及其配体排斥导向分子C(RGMc)在癌组织中的表达水平及其与临床病理学特征的关系。使用Cox回归分析评估探讨Neogenin、RGMc在NSCLC患者预后中的临床价值。并采用质粒构建及体外转染模型,利用共聚焦显微镜技术初步研究Neogenin参与NSCLC形成的可能机制。结果:Neogenin在NSCLC组织中表达明显下调(P<0.05)。RGMc在正常组织与癌组织中的表达并无明显差异;Neogenin表达下调与病理组织学分级、临床分期及患者不良预后显著相关(P<0.05)。体外细胞转染模型显示Neogenin通过调控胞内RGMc的转运及分布参与了RGMc介导的相关信号通路。结论:Neogenin作为抑癌基因在NSCLC组织中低表达且与患者预后显著相关。其机制可能与调控其配体RGMc在胞内的转运有关。本研究为后续深入探讨Neogenin作为抑癌基因参与NSCLC形成的分子机制研究奠定了基础。
Objective:To investigate the expression of Neogenin in non-small cell lung cancer(NSCLC)tissue and its prognostic value in NSCLC patients,as well as the mechanism involved in the development of NSCLC.Methods:The sequencing data of The Cancer Genome Atlas(TCGA)was used to evaluate whether the expression level of Neogenin in NSCLC was different from that in adjacent normal tissues;the data from the KM-plotter database was obtained to predict the prognostic role of Neogenin in NSCLC and its different tissue subtypes.The clinicopathological data of real-world NSCLC was collected to explore the expression levels of Neogenin and its ligand,repulsive guidance molecular C(RGMc),in cancer tissues and their relationship with clinicopathological features.Cox regression analysis was used to evaluate the clinical value of Neogenin and RGMc in the prognosis of NSCLC patients.The related plasmids were constructed and transfected into 293T cell line.The fluorescence images were taken to observe the location of Neogenin and RGMc in the cells by confocal microscopy.Results:The expression of Neogenin was significantly down-regulated in NSCLC tissues(P<0.05).There was no significant difference in the expression of RGMc between normal tissue and cancer tissue;the down-regulation of Neogenin expression was significantly correlated with histopathological grade,clinical stage and poor prognosis of patients(P<0.05).In vitro cell experiments showed that Neogenin participated in the signaling pathways mediated by RGMc by regulating the transport and distribution of intracellular RGMc.Conclusion:Neogenin as a tumor suppressor gene is down-regulated in NSCLC tissues and is significantly related to the prognosis of patients.The mechanism may be related to regulating the transport of its ligand RGMc in cells.This study set a foundation for the subsequent exploration of the molecular mechanism of Neogenin as a tumor suppressor gene involved in the development of NSCLC.
作者
席子尧
李湘浪
张妮
毛明玉
欧海斌
刘羽
XI Ziyao;LI Xianglang;ZHANG Ni;MAO Mingyu;OU Haibin;LIU Yu(Dept.of Radiation and Medical Oncology,Zhongnan Hospital of Wuhan University,Hubei Key Laboratory of Tumor Biological Behaviors,Hubei Cancer Clinical Study Center,&Hubei Cancer Radiation Therapy Quality Control Center,Wuhan 430071,Hubei,China)
出处
《武汉大学学报（医学版）》
CAS
2023年第6期699-705,共7页
Medical Journal of Wuhan University
基金
国家自然科学基金资助项目(编号:81001099,81370070,8217103238)
武汉大学中南医院科技创新培育基金(编号:cxpy2017027)
医学科技创新平台支撑项目(编号:PTXM2019030)。
