International journal of genomics
Identification of a Novel Subtype-Derived Prognostic Signature Based on Nucleotide Metabolism-Related Molecular Classification for Predicting Lung Adenocarcinoma Prognosis
Por Shi Y, Li S, Zhao L y 10 más.
Contenido en inglés
Resumen
Background
Lung adenocarcinoma (LUAD) is a major subtype of nonsmall cell lung cancer with substantial clinical heterogeneity. Nucleotide metabolism-related genes may contribute to tumor progression and immune microenvironment remodeling, but their prognostic value in LUAD remains incompletely defined.
Methods
Bulk transcriptomic and clinical data from TCGA-LUAD and GEO datasets were analyzed to define nucleotide metabolism-related molecular subtypes and construct a subtype-derived prognostic signature from subtype-associated differentially expressed genes. The TCGA-LUAD cohort was randomly divided into a training cohort and an internal validation cohort at a ratio of 4:1. Univariate Cox regression and LASSO regression analyses were performed exclusively in the training cohort to construct the prognostic signature, which was subsequently evaluated in the internal validation cohort and the independent external bulk-transcriptomic GSE30219 cohort. Consensus clustering, survival analysis, ROC analysis, immune infiltration analysis, mutation analysis, predicted drug sensitivity analysis, and exploratory single-cell transcriptomic characterization were also performed. In vitro assays were used to evaluate the functional relevance of IRX5 in A549 LUAD cells.