Integrated single-cell and bulk transcriptomic analysis reveals an epithelial cell-derived prognostic and immunotherapeutic signature with ADAM12 as a key functional regulator in non-small cell lung cancer.

This study developed a Prognostic and Immunotherapeutic Signature (PIS) for NSCLC using single-cell and bulk RNA-seq data. By integrating TCGA and GEO datasets with machine learning, we identified key epithelial cells-related genes predictive of immunotherapy response. PIS effectively stratifies patients by survival and immune activity, with low-PIS individuals showing better outcomes and higher immune infiltration. We confirmed the high expression of ADAM12 in both tissue samples and cell lines, and validated its functional roles through cellular assays. Furthermore, mouse model experiments demonstrated that knockout ADAM12 enhances the efficacy of immunotherapy. In summary, these findings establish ADAM12 as a critical oncogenic driver and a candidate therapeutic target in NSCLC that warrants further validation, while also providing a robust tool for guiding personalized immunotherapy.