The nAChR gene signature and LYPD3 in lung adenocarcinoma: prognosis and function

This study aims to construct a prognostic model for lung adenocarcinoma (nAChR) based on nicotinic acetylcholine receptor (nAChR) signaling pathway-related genes (NPRGs) and to investigate the role of the core gene LYPD3. By integrating transcriptomic and clinical data from TCGA, GEO, and GTEx databases, we identified NPRGs associated with overall survival and classified patients into two subtypes with significant prognostic differences. Using LASSO and multivariate Cox regression, we constructed a prognostic risk model (NRSM) (5-year AUC = 0.685) comprising seven genes (FMO3, MAOB, CYP2D6, DHRS7, CHRNB4, LYPD3, KLF4). The model effectively distinguished high-risk from low-risk patients in both the training set and multiple independent validation cohorts, with the risk score serving as an independent prognostic factor. The high-risk group was associated with higher tumor mutational burden and greater predicted sensitivity to EGFR inhibitors. Among these genes, LYPD3 overexpression was significantly correlated with poor patient prognosis, advanced clinical stage, and lymph node metastasis. Pathway enrichment analysis indicated its involvement in processes such as epithelial-mesenchymal transition (EMT). In vitro experiments further confirmed that LYPD3 knockdown significantly suppressed LUAD cell proliferation, migration, and invasion capabilities. This study successfully established a prognostic model for NPRGs with significant predictive value and identified LYPD3 as a key driver gene in the progression of LUAD, positioning it as a potential prognostic biomarker and therapeutic target.