ArticleCurrent issues in molecular biology2025
PAICS-Driven Purine Biosynthesis and Its Prognostic Implications in Lung Adenocarcinoma: A Novel Risk Stratification Model and Therapeutic Insights.
Article in Current issues in molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Abstract
backgroundLung adenocarcinoma is the most common NSCLC and is associated with metabolic dysregulation. Purine biosynthesis, regulated by PAICS, plays a key role in tumor progression and therapy resistance.
methodsWe focused on LUAD using pan-cancer and KEGG enrichment analyses. TCGA-LUAD and three GEO datasets were analyzed to confirm the prognostic relevance of purine biosynthesis. A prognostic model, the Purine Biosynthesis-Related Score (PBRS), was developed using LASSO regression and validated in independent cohorts. Gene set variation analysis, immune profiling, tumor mutational burden analysis, and drug sensitivity analysis were conducted. PAICS expression was validated in LUAD tissues, and its role was assessed via proliferation and migration assays.
resultsPBRS classified LUAD patients into high-risk (PBRS-high) and low-risk (PBRS-low) subgroups, with distinct prognostic outcomes. PBRS-high patients showed enrichment in cell cycle regulation and DNA repair pathways and had higher TMB, suggesting potential sensitivity to immunotherapy, although immune escape mechanisms may limit the efficacy of immune checkpoint inhibitors. PBRS-low patients were more responsive to metabolic inhibitors. PAICS overexpression correlated with poor prognosis, while its knockdown suppressed LUAD progression.
conclusionPBRS is a prognostic tool in LUAD, identifying PBRS-high patients who may benefit from immunotherapy or DDR-targeted therapies. PBRS-low patients exhibit sensitivity to metabolic inhibitors. PAICS is a potential therapeutic target.
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