Purine metabolism in lung adenocarcinoma: A single‐cell analysis revealing prognostic and immunotherapeutic insights

Abstract

AbstractLung adenocarcinoma (LUAD) is a prevalent subtype of lung cancer, yet the contribution of purine metabolism (PM) to its pathogenesis remains poorly elucidated. PM, a critical component of intracellular nucleotide synthesis and energy metabolism, is hypothesized to exert a significant influence on LUAD development. Herein, we employed single‐cell analysis to investigate the role of PM within the tumour microenvironment (TME) of LUAD. PM scoring (PMS) across distinct cell types was determined using AUCell, UCell, singscore and AddModuleScore algorithms. Subsequently, we explored communication networks among cells within high‐ and low‐PMS groups, establishing a robust PM‐associated signature (PAS) utilizing a comprehensive dataset comprising LUAD samples from TCGA and five GEO datasets. Our findings revealed that the high‐PMS group exhibited intensified cell interactions, while the PAS, constructed using PM‐related genes, demonstrated precise prognostic predictive capability. Notably, analysis across the TCGA dataset and five GEO datasets indicated that low‐PAS patients exhibited a superior prognosis. Furthermore, the low‐PAS group displayed increased immune cell infiltration and elevated CD8A expression, coupled with reduced PD‐L1 expression. Moreover, data from eight publicly available immunotherapy cohorts suggested enhanced immunotherapy outcomes in the low‐PAS group. These results underscore a close association between PAS and tumour immunity, offering predictive insights into genomic alterations, chemotherapy drug sensitivity and immunotherapy responses in LUAD. The newly established PAS holds promise as a valuable tool for selecting LUAD populations likely to benefit from future clinical stratification efforts.