PAICS-Driven Purine Biosynthesis and Its Prognostic Implications in Lung Adenocarcinoma: A Novel Risk Stratification Model and Therapeutic Insights
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View abstract on PubMed
Summary
This summary is machine-generated.A novel Purine Biosynthesis-Related Score (PBRS) predicts outcomes in lung adenocarcinoma (LUAD). High-risk LUAD patients may benefit from immunotherapy, while low-risk patients respond to metabolic inhibitors, highlighting PAICS as a therapeutic target.
Area Of Science
- Oncology
- Molecular Biology
- Bioinformatics
Background
- Lung adenocarcinoma (LUAD) is a major non-small cell lung cancer (NSCLC) subtype characterized by metabolic dysregulation.
- Purine biosynthesis, orchestrated by phosphoribosylaminoimidazole synthetase (PAICS), is critical for LUAD progression and therapeutic resistance.
Purpose Of The Study
- To develop and validate a prognostic model for LUAD based on purine biosynthesis pathways.
- To investigate the potential of this model and PAICS as therapeutic targets.
Main Methods
- Utilized pan-cancer and KEGG enrichment analyses on TCGA-LUAD and GEO datasets.
- Developed a Purine Biosynthesis-Related Score (PBRS) using LASSO regression and validated it in independent cohorts.
- Performed gene set variation, immune, tumor mutational burden, and drug sensitivity analyses; validated PAICS expression and function in LUAD models.
Main Results
- PBRS effectively stratified LUAD patients into high-risk and low-risk subgroups with distinct prognoses.
- High-risk patients exhibited enrichment in cell cycle and DNA repair pathways, with higher tumor mutational burden (TMB), suggesting potential immunotherapy response.
- Low-risk patients demonstrated sensitivity to metabolic inhibitors, and PAICS overexpression correlated with poor prognosis, with knockdown suppressing LUAD progression.
Conclusions
- PBRS serves as a valuable prognostic tool for LUAD, identifying patients who may benefit from immunotherapy or DNA damage repair (DDR)-targeted therapies.
- PBRS-low patients show promise for metabolic inhibitor treatment, and PAICS emerges as a potential therapeutic target for LUAD.
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