摘要
目的通过分析蛋白磷酸酶2A催化亚基α(PPP2CA)在结直肠癌(CRC)中表达水平与患者预后及免疫浸润的关系,进一步了解CRC发生和进展中的相关机制。方法基于基因芯片数据库Oncomine和肿瘤免疫评估资源(TIMER)数据库分析在CRC组织和正常组织中PPP2CA表达水平的差异性;基于阿拉巴马大学伯明翰分校癌症数据分析门户(UALCAN)和基因表达谱交互分析(GEPIA)数据库分析PPP2CA的表达水平对CRC患者预后的影响;基于LinkedOmics平台构建PPP2CA的共表达网络并进行基因本体论(GO)富集分析和京东基因和基因组百科全书(KEGG)通路分析;基于TIMER和GEPIA数据库分析PPP2CA与免疫浸润之间的相关性。基于c-BioPortal平台分析结肠腺癌(COAD)中PPP2CA的基因突变情况。结果与正常结直肠组织相比,在CRC组织中PPP2CA表达下调。高表达水平的PPP2CA预示着更好的总生存期(OS)和无进展生存期(PFS)。在COAD中,PPP2CA的表达水平与包括CD8^(+)T细胞、中性粒细胞和树突状细胞在内的免疫浸润细胞呈正相关。而某些免疫细胞标志物,包括B细胞的CD19和CD38、M1巨噬细胞的一氧化氮合酶2(NOS2)、M2巨噬细胞的精氨酸酶1(Arg1)和甘露糖受体C1(MRC1)、肿瘤相关巨噬细胞(TAM)的人类白细胞抗原G(HLA-G)和CD80、单核细胞的CD14和IgG Fc段受体Ⅲa(FCGR3A),却显示出不同的PPP2CA相关免疫浸润模式:即PPP2CA表达水平与COAD和直肠腺癌(READ)中的B细胞、巨噬细胞、单核细胞、TAM、1型辅助T(Th1)细胞、Th2细胞、调节性T细胞、衰竭T细胞和中性粒细胞均显著相关。结论PPP2CA在CRC组织表达水平下调,并且与免疫浸润密切相关。
Objective To analyze the relationship between protein phosphatase 2A catalytic subunit alpha(PPP2CA)expression and prognosis and immune infiltration in colorectal cancer(CRC)patients,and further explore the mechanism about the development and progression of CRC.Methods The differences in PPP2CA expression levels between CRC tissues and normal tissues were analyzed using the gene chip database Oncomine and The Tumor Immune Estimation Resource(TIMER)database.The impact of PPP2CA expression levels on the prognosis of CRC patients was analyzed using The University of Alabama at Birmingham Cancer data analysis portal(UALCAN)and Gene Expression Profiling Interactive Analysis(GEPIA)databases.To further understand the role of PPP2CA in CRC,the co-expression network of PPP2CA was constructed using LinkedOmics platform,followed by Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Besides,the correlation between PPP2CA and immune infiltration was analyzed using TIMER and GEPIA databases.The gene mutation of PPP2CA in colon adenocarcinoma(COAD)were analyzed using c-BioPortal platform.Results PPP2CA was down-regulated in CRC tissues compared with normal tissues,and higher PPP2CA expression indicated better Overall Survival(OS)and Progression-Free Survival(PFS).In COAD,the expression level of PPP2CA was positively correlated with immune infiltrating cells including CD8^(+)T cells,neutrophils and dendritic cells.However,certain immune cell markers including CD19 and CD38 in B cells,NOS2 in M1 macrophages,Arginase 1(ARG1)and Mannose Receptor C-Type 1(MRC1)in M2 macrophages,Human Leukocyte Antigen G(HLA-G)and CD80 in Tumor Associated Macrophage(TAM)and CD14 and Fc Gamma Receptor 3A(FCGR3A)in monocytes,showed a different pattern of PPP2CA-associated immune infiltration.In other words,PPP2CA expression level was significantly associated with B cells,macrophages,monocytes,TAM,Th1 cells,Th2 cells,regulatory T cells,exhausted T cells and neutrophils in both COAD and rectum adenocarcinoma(READ).Conclusion PPP2CA is down-regulated in CRC tissues and closely correlated with immune infiltration.
作者
梁小洁
程照翔
尚维伟
陈信浩
李俊
LIANG Xiaojie;CHENG Zhaoxiang;SHANG Weiwei;CHEN Xinhao;LI Jun(Department of General Surgery,Affiliated Jiangning Hospital of Nanjing Medical University,Nanjing 211100;Department of General Surgery,Nanjing Jiangning Hospital of Chinese Medicine,Nanjing 211100;Department of Hepatopancreatobiliary Surgery,Affiliated Jiangning Hospital of Nanjing Medical University,Nanjing 211100,China)
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2024年第7期591-604,共14页
Chinese Journal of Cellular and Molecular Immunology
基金
南京市医学科技发展项目(YKK21231,QRX17102)
南京市科技计划项目(201803071)
南京医科大学科技发展项目(NMUB20210155)。
