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[摘要]
目的:探讨蛋白酶体激活亚基3(proteasome activator complex subunit 3,PSME3)在胃癌(gastric cancer,GC)组织中的 表达及其与患者预后的相关性,分析其在GC发生发展中的作用及其机制。方法:利用TCGA和UALCAN等数据库资料分析 PSME3基因在GC组织中的表达。用qPCR法验证2017年1月至2018年12月河北医科大学第四医院手术切除的40例GC患者 的癌及癌旁组织中PSME3的表达。用ROC曲线和Kaplan-Meier plotter分析数据库中数据PSME3在GC诊断和预后预测中的价 值,进一步分析PSME3主要参与的生物过程和所涉及的信号通路。结果:PSME3在GC组织中的表达水平显著高于癌旁组织, 且与GC患者的肿瘤分期、病理亚型、淋巴结转移状态和是否感染幽门螺旋杆菌显著相关(均P<0.01)。qPCR验证性检测课题组 收集的GC组织标本中PSME3同样呈高水平表达(P<0.01)。PSME3区分GC患者和正常人群的AUC值为0.808,PSME3低表达 组GC患者的总生存期、首次进展生存期和进展后生存期均长于PSME3低表达组的GC患者(均P<0.01)。PSME3主要通过调控 细胞周期以及mTORC1、 PI3K/AKT/mTOR和TGF-β信号通路等而在GC的发生发展中发挥致癌基因的作用。结论:PSME3在 GC组织中显著高表达,且与GC患者的不良预后显著相关, 在GC的发生发展中发挥致癌基因的作用。
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[Abstract]
Objective: To explore the expression of PSME3 (proteasome activator complex subunit 3) in gastric cancer (GC) tissues and its correlation with the prognosis of GC patients, and tofurtheranalyzeitseffect and mechanism in the occurrence and development of GC. Methods: The expression level of PSME3 gene in GC tissues was analyzed with TCGA and UALCAN database. qPCR was used to verify the expression of PSME3 in GC tissues and corresponding adjacent normal tissues that resected from 40 GC patients who were surgically treated in the Fourth Hospital ofHebeiMedicalUniversityfromJanuary2017toDecember 2018. ROC curve and KaplanMeier plotter method were used to analyzethevalueofPSME3mainlyindiagnosingandpredictingtheprognosis of GC patients. The biological processes and pathways that PSME3 involved in were further analyzed. Results: The expression level of PSME3 in GC tissues was significantly higher than that in normal tissues, and it’s high expression was significantly correlated with the tumor stage, pathological subtype, status of lymph node metastasis and Helicobacter pylori infection in GC patients (all P<0.01). PSME3 was also highly expressed in GC tissue samples collected by the qPCR confirmatory detection group (P<0.01). PSME3 could distinguish gastric cancer patients from normal people with an AUC value of 0.808. The overall survival time, the first progression survival time and post progression survival time of the GC patients with low PSME3 expression were longer than those in the patients with high PSME3 expression (all P<0.01). Mechanism research found that PSME3 mainly played an oncogenic role of the development of GC by regulating cell cycle, mTORC1 signaling pathway, PI3K/AKT/mTOR signaling pathway and TGF-β signaling pathway etc. Conclusion: PSME3 is highly expressed in GC tissues, and it is significantly related to the poor prognosis of GC patients. It plays an oncogenic role in the occurrence and development of GC.
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