Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.