Stemness-associated WNT3A and EDN3 as key regulators of tumor progression and immunotherapy efficacy in LUAD

Lung adenocarcinoma (LUAD) is a common and aggressive cancer. Stemness-related genes may play key roles in tumor progression and immune response, but their specific contributions in LUAD remain unclear.

Differential expression analysis, WGCNA, and survival analysis were used to study WNT3A and EDN3 in LUAD. GSEA was performed to explore biological pathways associated with WNT3A. Immune infiltration analysis evaluated the tumor microenvironment, and immunotherapy response was assessed. Experimental validation was conducted using qPCR and Western Blot on lung cancer cell lines.

WNT3A and EDN3 expression were significantly correlated with LUAD patient survival and showed high diagnostic value. GSEA revealed that high WNT3A expression activated pathways involved in tumor proliferation, metabolism, and immune escape. Patients with high WNT3A expression had lower macrophage infiltration and higher immune scores. Immunotherapy analysis showed better response rates in patients with high WNT3A expression, while EDN3 had no significant association. qPCR and Western Blot confirmed low WNT3A and EDN3 expression in lung cancer cells.

WNT3A and EDN3 are potential prognostic biomarkers for LUAD. WNT3A, in particular, is associated with enhanced immunotherapy response, making it a promising target for future clinical applications.