PPP2R1A作为肺腺癌潜在预后标志物的研究  

Study of PPP2R1A as a potential progonstic biomarker for lung adenocarcinoma

作　　者：白静 王卓灵 刘菲 刘美麟 韩继明[1] 张华华 BAI Jing;WANG Zhuoling;LIU Fei;LIU Meilin;HAN Jiming;ZHANG Huahua(Medical Research and Experimental Center,Yan′an University,Yan′an 716000,China;Department of Infectious Diseases,First Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710000,China)

机构地区：[1]延安大学医学研究实验中心,陕西延安716000 [2]西安交通大学第一附属医院感染科,陕西西安710000

出　　处：《延安大学学报(医学科学版)》2025年第1期1-9,共9页Journal of Yan'an University:Medical Science Edition

基　　金：陕西省自然科学基础研究计划一般项目(2024JC-YBMS-683);陕西省教育厅专项科研计划项目(23JK0735);省级大学生创新创业训练计划项目(S202410719136)。

摘　　要：目的本研究旨在探讨蛋白磷酸酶2支架亚基Aalpha(Protein phosphatase 2 scaffold subunit Aalpha,PPP2R1A)在肿瘤发生、进展及免疫治疗中的作用。方法多种生物信息学数据库分析PPP2R1A在泛癌中的表达、与肿瘤免疫的关系及其与肿瘤预后的相关性。生物信息学分析联合Western blot实验检测PPP2R1A在肺腺癌(Lung adenocarcinoma,LUAD)中的表达,并设计靶向PPP2R1A的小干扰RNA,评估其对LUAD细胞增殖、迁移能力的影响。利用LinkedOmics数据库分析LUAD中PPP2R1A的相关基因及其潜在功能。结果PPP2R1A在包含LUAD在内的12种肿瘤组织中表达升高,在胶质母细胞瘤等4种肿瘤中表达下调。PPP2R1A的表达与多种肿瘤的免疫浸润相关,且PPP2R1A的表达与包括LUAD在内的6种肿瘤的肿瘤突变负荷(Tumor mutation burden,TMB)呈正相关,并与LUAD等5种肿瘤的微卫星不稳定性(Microsatellite Instability,MSI)呈正相关。体外实验显示PPP2R1A在LUAD中高表达,且沉默PPP2R1A显著抑制LUAD细胞的增殖与迁移。KEGG信号通路富集分析显示:与PPP2R1A呈正相关的通路主要富集于核糖体、剪接体、蛋白酶体等;而与PPP2R1A呈负相关的通路主要富集于Ⅰ型糖尿病、哮喘、Th17细胞分化等。GO功能结果显示,PPP2R1A在生物学过程中主要富集于生物调节和代谢过程等;在细胞中主要富集于细胞膜与细胞核等;在分子功能方面主要富集于蛋白质结合和离子结合等。结论PPP2R1A是潜在的癌症特别是LUAD的预后标志物。本研究提出了旨在靶向LUAD中PPP2R1A的前瞻性治疗策略,并为肿瘤靶向治疗提供了新的线索。Objective This study aimed to examine the role of the protein phosphatase 2 scaffold subunit Aalpha(PPP2R1A)in tumorigenesis,cancer progression,and response to immunotherapy.Methods The expression of PPP2R1A across various cancer types,its association with tumor immunity,and its correlation with tumor prognosis were systematically analyzed using multiple bioinformatics databases.In the context of lung adenocarcinoma(LUAD),the expression levels of PPP2R1A were detected by bioinformatics analyses combined with western blot experiments. Additionally, small interfering RNAs targeting PPP2R1A were designed to investigate their impact on the proliferation and migratory capabilities of LUAD cells. Furthermore, the LinkedOmics database was employed to explore the genes associated with PPP2R1A and their potential functional roles in LUAD. Results The expression of PPP2R1A was found to be elevated in 12 tumor tissues, including LUAD, while it was down-regulated in 4 tumors, including glioblastoma. Furthermore, PPP2R1A expression demonstrated a correlation with immune infiltration across multiple tumor types. Notably, PPP2R1A expression exhibited a positive correlation with tumor mutation burden (TMB) in 6 tumors, including LUAD, and a positive correlation with microsatellite instability (MSI) in 5 tumors, also including LUAD. In vitro experiments indicated that PPP2R1A was highly expressed in LUAD, and the silencing of PPP2R1A significantly inhibited the proliferation and migration of LUAD cells. Enrichment analysis of KEGG signaling pathways revealed that pathways positively correlated with PPP2R1A were predominantly associated with ribosomes, spliceosomes, and the proteasome, etc. Conversely, pathways negatively correlated with PPP2R1A were primarily enriched in type I diabetes mellitus, asthma, and Th17 cell differential, etc. The results of the GO functional analysis reveal that PPP2R1A is chiefly enriched in the categories of biological regulation and metabolic processes within the biological process domain. In the ce

关 键 词：蛋白磷酸酶2支架亚基Aalpha 泛癌 肺腺癌 增殖和迁移 

分 类 号：R734[医药卫生—肿瘤]