Xiao Shanshan, Hu Yuhong, Li Yawen, Zhang Xin, Xiao Zijun, Dong Mingyou, Liao Lusheng
Obstetrics and Gynecology Department, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Guangxi Engineering Research Center for Precise Genetic Testing of Long-dwelling Nationalities, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Front Immunol. 2025 Dec 2;16:1652629. doi: 10.3389/fimmu.2025.1652629. eCollection 2025.
Lung adenocarcinoma (LUAD) is a major subtype of lung cancer with poor prognosis. The protein phosphatase 2 regulatory subunit A alpha (PPP2R1A) plays complex roles in tumorigenesis, but its function and clinical significance in LUAD remain unclear.
We analyzed PPP2R1A expression across cancers using the Xiantao Academic Online tool and TCGA data. Diagnostic potential was evaluated via ROC curve analysis. Prognostic value was assessed using Kaplan-Meier survival and Cox regression analyses. Protein-protein interaction networks and functional enrichment analyses were conducted to explore molecular mechanisms. Immune infiltration patterns were investigated using TIMER2.0. Experimental validation was performed through CRISPR/Cas9-mediated knockdown in A549 cells, followed by functional assays including CCK-8, clonogenic, wound healing, and Transwell assays.
PPP2R1A was significantly upregulated in LUAD tissues compared to normal controls (P < 0.05). It demonstrated modest diagnostic value with an AUC of 0.593. High PPP2R1A expression was associated with poor progression-free survival (FP) and overall survival (OS), particularly in early-stage disease. PPP2R1A expression correlated with advanced N stage and tumor stage. Functional enrichment analysis revealed involvement in protein dephosphorylation, cell cycle regulation, and metabolic pathways. Immune infiltration analysis showed significant correlations with macrophage and CD4+ T cell infiltration. Experimental validation confirmed that PPP2R1A knockdown significantly inhibited LUAD cell proliferation, migration, and invasion (P < 0.01).
PPP2R1A is overexpressed in LUAD and associated with poor prognosis, potentially serving as an oncogene by regulating key signaling pathways and immune microenvironment. Its knockdown suppresses malignant phenotypes, highlighting its potential as both a prognostic biomarker and therapeutic target in LUAD.
肺腺癌（LUAD）是肺癌的一种主要亚型，预后较差。蛋白磷酸酶2调节亚基Aα（PPP2R1A）在肿瘤发生中发挥复杂作用，但其在LUAD中的功能和临床意义仍不清楚。
我们使用仙桃学术在线工具和TCGA数据分析了PPP2R1A在各种癌症中的表达情况。通过ROC曲线分析评估其诊断潜力。使用Kaplan-Meier生存分析和Cox回归分析评估预后价值。进行蛋白质-蛋白质相互作用网络和功能富集分析以探索分子机制。使用TIMER2.0研究免疫浸润模式。通过CRISPR/Cas9介导的A549细胞敲低进行实验验证，随后进行包括CCK-8、克隆形成、伤口愈合和Transwell实验在内的功能测定。
与正常对照相比，PPP2R1A在LUAD组织中显著上调（P < 0.05）。其诊断价值中等，AUC为0.593。PPP2R1A高表达与无进展生存期（PFS）和总生存期（OS）较差相关，尤其是在早期疾病中。PPP2R1A表达与晚期N分期和肿瘤分期相关。功能富集分析显示其参与蛋白质去磷酸化、细胞周期调控和代谢途径。免疫浸润分析显示与巨噬细胞和CD4+ T细胞浸润显著相关。实验验证证实，PPP2R1A敲低显著抑制LUAD细胞增殖、迁移和侵袭（P < 0.01）。
PPP2R1A在LUAD中过表达并与不良预后相关，可能通过调节关键信号通路和免疫微环境作为癌基因发挥作用。其敲低可抑制恶性表型，突出了其作为LUAD预后生物标志物和治疗靶点的潜力。
