微管相关蛋白4在胰腺癌组织中的表达及其临床意义  

Expression and clinical significance of microtubule-associated protein 4 in pancreatic adenocarcinoma tissues

作　　者：左龙燕 梁应飞 咸新苗 亓同钢[1] ZUO Longyan;LIANG Yingfei;XIAN Xinmiao;QI Tonggang(Central Research Laboratory,the Second Hospital of Shandong University,Jinan 250033,Shandong;Department of Pathology,Liaocheng People′s Hospital,Liaocheng 252000,Shandong,China;Department of Medical Laboratory,Liaocheng People′s Hospital,Liaocheng 252000,Shandong,China;Department of Precision Medicine Laboratory,Liaocheng People′s Hospital,Liaocheng 252000,Shandong,China)

机构地区：[1]山东大学第二医院中心实验室,济南250033 [2]聊城市人民医院,病理科,山东聊城252000 [3]聊城市人民医院,检验科,山东聊城252000 [4]聊城市人民医院,精准医学重点实验室,山东聊城252000

出　　处：《临床检验杂志》2025年第3期185-192,共8页Chinese Journal of Clinical Laboratory Science

基　　金：山东省自然科学基金面上项目(ZR202MH224)。

摘　　要：目的 探讨微管相关蛋白4(microtubule-associated protein 4,MAP4)在胰腺癌(pancreatic adenocarcinoma,PAAD)患者组织中的表达水平及其临床意义。方法 采用免疫荧光技术检测于聊城市人民医院就诊的60例PAAD患者组织中MAP4的表达水平。获取TCGA和GTEx数据库中179例PAAD组织和332例正常胰腺组织的转录组数据,分析 MAP4 mRNA的表达水平及其与患者预后的关系。通过生信分析MAP4的表达水平与肿瘤干性指标、肿瘤浸润免疫细胞以及免疫检查点的相关性。使用小干扰RNA技术沉默PAAD细胞系MiaPaCa-2和PANC-1中MAP4的表达,并通过CCK-8和Transwell试验评估其对细胞增殖、迁移和侵袭能力的影响。结果 免疫荧光技术结果显示,MAP4在PAAD组织中的表达水平显著高于正常胰腺组织(P<0.05)。生信分析结果表明, MAP4 mRNA在PAAD组织中的表达水平显著上调(P<0.05),且其高表达与患者较短的无病间期和无进展间隔显著相关(P<0.05)。MAP4的表达水平与RNA相关肿瘤干性指数呈显著负相关(r=-0.55,P<0.05),但与巨噬细胞和树突状细胞浸润呈显著正相关(r>0.5,P<0.05)。体外实验结果证实,沉默MAP4显著抑制了PAAD细胞的增殖、迁移和侵袭能力(P<0.05)。结论 MAP4在PAAD组织中呈高表达,其表达水平与患者预后、肿瘤干性和免疫细胞浸润密切相关。MAP4通过调节肿瘤细胞生物学行为和免疫微环境参与PAAD的进展,为PAAD的诊断和治疗提供了潜在的新靶点。Objective To investigate the expression pattern and clinical significance of microtubule-associated protein 4(MAP4)in pancreatic adenocarcinoma(PAAD).Methods The immunofluorescence technique was used to detect the expression level of MAP4 in the tissues from 60 PAAD patients visited Liaocheng People′s Hospital.The expression levels of MAP4 mRNA and their correlations with patients′prognosis were analyzed using the transcriptome data from 179 PAAD and 332 normal pancreatic tissues in the TCGA and GTEx databases.The correlations of the expression levels of MAP4 with tumor stemness indices,tumor-infiltrating immune cells,and immune checkpoints were analyzed by the bioinformatics method.The small interfering RNA technology was used to silence the expression of MAP4 in PAAD cell lines such as MiaPaCa-2 and PANC-1,and its effects on cell proliferation,migration,and invasion abilities were evaluated by the CCK-8 and Transwell assays.Results The results of immunofluorescence showed that the expression levels of MAP4 in PAAD tissues were significantly higher than that in normal pancreatic tissues(P<0.05).The bioinformatics analysis indicated that the expression levels of MAP4 mRNA in PAAD tissues were significantly up-regulated(P<0.05),and that their high expression was significantly correlated with shorter disease-free and progression-free intervals in patients(P<0.05).The expression levels of MAP4 were significantly negatively correlated with RNA-related tumor stemness indices(r=-0.55,P<0.05),but significantly positively correlated with macrophage and dendritic cell infiltration(r>0.5,P<0.05).In vitro experimental results confirmed that silencing MAP4 could significantly inhibit the proliferation,migration,and invasion abilities of PAAD cells(P<0.05).Conclusion MAP4 is highly expressed in PAAD tissues,and its expression levels are closely related to patients′prognosis,tumor stemness,and immune cell infiltration.MAP4 may participate in the progression of PAAD by regulating the biological behavior and immune microen

关 键 词：微管相关蛋白4 胰腺癌 肿瘤干性 免疫浸润 

分 类 号：R446[医药卫生—诊断学] R735.9[医药卫生—临床医学]