自噬相关基因5在人恶性胸膜间皮瘤中的表达及其意义  

Expression and significance of autophagy-related gene 5 in human malignant pleural mesothelioma

作　　者：刘如爱 王播勇 李锦松 普元倩 余敏 熊伟 LIU Ruai;WANG Boyong;LI Jinsong;PU Yuanqian;YU Min;XIONG Wei(Department of Biochemistry and Molecular Biology,College of Basic Medical Sciences,Dali University,Dali 671000,China;Key Laboratory of Clinical Biochemical Testing in Yunnan Provincial Universities,Dali 671000,China;Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D,Dali 671000,China;Laboratory of Biochemistry and Molecular Biology,School of Life Sciences,Yunnan University,Kunming 650091,China)

机构地区：[1]大理大学基础医学院生物化学与分子生物学教研室,云南大理671000 [2]云南省高校临床生物化学检验重点实验室,云南大理671000 [3]云南省昆虫生物医药研发重点实验室,云南大理671000 [4]云南大学生命科学学院生物化学与分子生物学实验室,昆明650091

出　　处：《中国医科大学学报》2024年第8期673-679,共7页Journal of China Medical University

基　　金：国家自然科学基金(82160516);云南省昆虫生物医药研发重点实验室开放课题(AG2022003);云南省教育厅科学研究基金(2023Y0949)。

摘　　要：目的探讨自噬相关基因5(ATG5)在人恶性胸膜间皮瘤(MPM)细胞和组织中的表达情况,分析ATG5与MPM患者临床病理参数和预后的相关性。方法实时定量PCR(RT-qPCR)和Western blotting检测正常人胸膜间皮细胞和MPM细胞、非MPM胸膜间皮组织和MPM组织中ATG5的表达差异。应用TCGA数据库分析ATG5与MPM患者临床病理特征和预后的相关性。构建Cox回归模型,分析影响MPM患者预后的因素。GEPIA数据库评估ATG5与MPM肿瘤标志物和新型血清标志物的相关性。TIMER数据库分析ATG5与MPM免疫细胞浸润和关键免疫调节基因的相关性。结果ATG5在MPM细胞和组织中显著高表达,且与MPM患者的肿瘤分期呈正相关(P<0.05)。生存分析显示,ATG5高表达组MPM患者的预后更差,肿瘤病理类型可能是患者预后不良的危险因素(P<0.05)。ATG5与多种MPM肿瘤标志物(MTAP、SETD2、NF2、FIB3)和新型血清标志物(HMGB1、SMPR、THBS2、KRAS)显著相关(P<0.05)。ATG5表达与MPM中免疫细胞浸润(B细胞、CD4^(+)T细胞和巨噬细胞)和免疫相关基因(CD28、CUL48B、CD166、MMP14)呈显著正相关(P<0.05)。结论ATG5在MPM中表达上调,且与患者不良预后和免疫浸润水平相关,有望成为MPM早期筛查、诊断和预后评估的重要生物标志物。Objective To explore the expression of autophagy-related gene 5(ATG5)in human malignant pleural mesothelioma(MPM)cells and tissues and analyze the correlation between ATG5 expression and patient clinicopathological parameters and prognosis.Methods Real-time quantitative PCR and Western blotting were used to detect differences in ATG5 expression between normal human pleural mesothelial cells and MPM cells and between non-MPM pleural mesothelial tissues and MPM tissues.The Cancer Genome Atlas was used to analyze correlations between ATG5 expression and clinicopathological characteristics and prognosis of patients with MPM.A Cox proportional hazard model was constructed to analyze factors affecting the prognosis of patients with MPM.The Gene Expression Profiling Interactive Analysis database was used to evaluate the correlation between ATG5 and MPM tumor markers and novel serum markers.Tumor Immune Estimation Resource was used to analyze correlations between ATG5 and MPM immune cell infiltration and key immune regulatory genes.Results ATG5 was highly expressed in MPM cells and tissues and positively correlated with tumor stage(P<0.05).High ATG5 expression indicated poor prognosis(P<0.05).ATG5 expression was significantly associated with various MPM tumor markers(MTAP,SETD2,NF2,and FIB3)and novel serum markers(HMGB1,SMPR,THBS2,and KRAS)(P<0.05).ATG5 was associated with immune cell infiltration in MPM(B cells,CD4^(+)T cells,and macrophages)and expression of immune-related genes(CD28,CUL48B,CD166,and MMP14)(P<0.05).Conclusion ATG5 is upregulated in MPM and is associated with poor prognosis and immune cell infiltration.ATG5 could be a key biomarker for early screening,diagnosis,and prognostic assessment of MPM.

关 键 词：恶性胸膜间皮瘤 自噬相关基因5 自噬 预后 免疫浸润 

分 类 号：R734.3[医药卫生—肿瘤]