Identification of a Glycosylation‐Related Gene Prognostic Signature for Non–Small Cell Lung Cancer
Qingtao Zhao, Xiaopeng Zhang, Guochen DuanABSTRACT
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.