Identification of a Glycosylation‐Related Gene Prognostic Signature for Non–Small Cell Lung Cancer

PURPOSE: A prognostic signature for non-small cell lung cancer (NSCLC) was developed through identification and integration of glycosylation-related genes (GRGs). METHODS: TCGA RNA-seq data for LUAD and LUSC were analyzed. GRGs were intersected with differentially expressed genes; prognostic GRGs were selected via Cox and LASSO regression to construct a risk model. The immune microenvironment and immunotherapy responses were compared between risk groups. An miRNA-mRNA-transcription factor (TF) network was built and potential drugs were predicted. ADAMTS15 expression was verified by RT-qPCR in NSCLC tissues and cell lines; functional assays (CCK-8, wound healing, Transwell) were performed after ADAMTS15 knockdown in A549 (LUAD) and NCI-H520 (LUSC) cells. RESULTS: A total of 134 differentially expressed GRGs were identified. Ten genes (ADAMTS15, PCSK9, MUC2, B3GNT3, etc.) were selected for the prognostic model, which functioned as an independent prognostic factor. High-risk patients showed poorer immunotherapy response. The regulatory network included 30 TFs and 142 miRNAs, with 107 drug-target pairs predicted. ADAMTS15 was elevated in NSCLC; its knockdown inhibited proliferation, migration, and invasion in both LUAD and LUSC cell models. CONCLUSION: A 10-gene prognostic signature derived from GRGs was identified. Functional validation affirmed ADAMTS15's tumor-promoting role, offering insights for NSCLC prognosis and targeted therapy.