α-1-酸性糖蛋白1在肺癌中的表达及其生物学功能探究

Expression and Biological Functions of Alpha-1-acid Glycoprotein 1 in Lung Cancer

α-1-酸性糖蛋白(alpha-1-acid glycoprotein 1, AGP1)属于orosomucoid家族成员,主要由肝细胞和中性粒细胞分泌,是相对分子质量为23.51 kD的酸性糖蛋白。前期研究发现, AGP1蛋白在早期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者血清中含量下降,有望作为NSCLC早诊标志物,但其在肺癌组织中的表达、具体生物学作用及临床意义尚不清楚。本研究运用GEPIA数据库分析肺癌组织中AGP1 m RNA的表达水平,采用蛋白质印迹法检测AGP1蛋白在肺癌组织和血清中的含量,利用cBioPortal数据库分析AGP1在肺癌组织中的DNA改变频率,利用STRING数据库构建与AGP1蛋白相互作用的蛋白质网络,利用HPA和Kaplan-Meier数据库分析AGP1的表达水平与肺癌患者生存的关系;同时,构建过表达AGP1基因的A549和H157肺癌细胞系,通过CCK-8实验检测过表达AGP1对A549和H157细胞增殖的影响。结果显示:AGP1的m RNA水平在486例肺鳞癌组织中显著下降,在早期肺癌组织和血清中AGP1的蛋白质表达水平也下降,而且AGP1低表达的肺癌患者生存时间短。在肺癌细胞中过表达AGP1基因后, A549细胞和H157细胞中AGP1蛋白的表达量显著增加,且过表达AGP1后A549和H157细胞的增殖受到显著抑制。在cBioPortal数据库的1 144例肺癌样本中, AGP1基因总的改变率是1.10%,其中在肺腺癌中的突变比例为0.91%,扩增比例为0.30%,缺失比例是0.30%;在肺鳞癌中的突变比例为0.41%,缺失比例是0.21%, DNA水平的改变可能是AGP1表达水平降低的原因之一。AGP1与ALB、FGG、A2M、FGB、FGA、HRG、SERPINA1、ORM2、AHSG和HP有相互作用。本研究阐明了AGP1基因在肺癌组织中的表达情况、对肺癌细胞增殖的抑制功能及其与生存的相关性,为其可能用于肺癌生存评估或作为治疗靶点提供了科学依据和数据支持。

Alpha-1-acid glycoprotein 1(AGP1)is a member of the orosomucoid family and is mainly secret-ed by hepatocytes and neutrophils.It is an acid glycoprotein with a relative molecular mass of 23.51 kD.Previous studies have found that the AGP1 level in sera of patients with early non-small cell lung cancer(NSCLC)is decreased,and it is expected to be used as a biomarker for early diagnosis of NSCLC.However,its expression,specific biological roles and clinical significance in lung cancer are still unclear.Herein,GEPIA database was used to analyze the expression changes of AGP1 mRNA in lung cancer tissues.Westernblot was used to detect the content of AGP1 in lung cancer tissues and sera.The DNA frequency changes of AGP1 in lung cancer tissues were analyzed by cBioPortal database.The protein network interacting with AGP1 was constructed by using STRING database.HPA and Kaplan-Meier databases were used to analyze the relationship between the expression of AGP1 and the survival of lung cancer patients.The A549 and H157 lung cancer cell lines overexpressing the AGP1 gene were constructed,and the effects of AGP1 overexpression on the proliferation of A549 and H157 cells were detected by CCK-8 experiments.The results showed that the mRNA levels of AGP1 were significantly decreased in 486 cases of lung squamous cell carcinoma tissues,and the levels of AGP1 in early lung cancer tissues and sera were also decreased.The lung cancer patients with lower AGP1 expression had a shorter survival time.The expression of AGP1 in lung cancer cell lines A549 and H157 was significantly increased and the proliferation of both cells was significantly inhibited after overexpression of the AGP1 gene.According to the analysis of 1144 lung cancer samples in cBioPortal database,the total change rate of AGP1 gene was 1.10%.In lung adenocarcinoma,the mutation rate was 0.91%,the amplification rate was 0.30%,and the deletion rate was 0.30%,while in lung squamous cell carcinoma,the mutation rate was 0.41%,and the deletion rate was 0.21%.The changes at the DNA level might be one of the reasons for the decrease of AGP1 expression level.Protein interaction network analysis revealed that AGP1 interacted with ALB,FGG,A2M,FGB,FGA,HRG,SERPINA1,ORM2,AHSG and HP.The above results clarified the expression changes of AGP1 gene in lung cancer and its correlation with survival and its biological functions,and may provide scientific basis and data support for its possible use in the survival assessment of lung cancer patients or as a therapeutic target.