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[蛋白质磷酸酶2A催化亚基α(PPP2CA)表达与结直肠癌患者预后及免疫浸润关系的生物信息学分析]

[Bioinformatic analysis of the relationship between protein phosphatase 2A catalytic subunit alpha (PPP2CA) expression and prognosis and immune infiltration in colorectal cancer patients].

作者信息

Liang Xiaojie, Cheng Zhaoxiang, Shang Weiwei, Chen Xinhao, Li Jun

机构信息

Department of General Surgery, Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China.

Department of General Surgery, Nanjing Jiangning Hospital of Chinese Medicine, Nanjing 211100, China.

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2024 Jul;40(7):591-604.

Abstract

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.

摘要

目的 分析蛋白磷酸酶2A催化亚基α(PPP2CA)表达与结直肠癌(CRC)患者预后及免疫浸润的关系,并进一步探讨CRC发生发展的机制。方法 使用基因芯片数据库Oncomine和肿瘤免疫评估资源(TIMER)数据库分析CRC组织与正常组织中PPP2CA表达水平的差异。使用阿拉巴马大学伯明翰分校癌症数据分析门户(UALCAN)和基因表达谱交互式分析(GEPIA)数据库分析PPP2CA表达水平对CRC患者预后的影响。为进一步了解PPP2CA在CRC中的作用,使用LinkedOmics平台构建PPP2CA的共表达网络,随后进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析。此外,使用TIMER和GEPIA数据库分析PPP2CA与免疫浸润的相关性。使用c-BioPortal平台分析结肠腺癌(COAD)中PPP2CA的基因突变情况。结果 与正常组织相比,CRC组织中PPP2CA表达下调,较高的PPP2CA表达表明总体生存期(OS)和无进展生存期(PFS)更好。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。然而,B细胞中的某些免疫细胞标志物包括CD19和CD38、M1巨噬细胞中的NOS2、M2巨噬细胞中的精氨酸酶1(ARG1)和甘露糖受体C型1(MRC1)、肿瘤相关巨噬细胞(TAM)中的人类白细胞抗原G(HLA-G)和CD80以及单核细胞中的CD14和Fcγ受体3A(FCGR3A),显示出与PPP2CA相关的免疫浸润的不同模式。换句话说,在COAD和直肠腺癌(READ)中,PPP2CA表达水平与B细胞、巨噬细胞、单核细胞、TAM、Th1细胞、Th2细胞、调节性T细胞、耗竭性T细胞和中性粒细胞均显著相关。结论 PPP2CA在CRC组织中表达下调且与免疫浸润密切相关。

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