Fig. 6

Exploration of biological characteristics of CDKN1A in advanced LUAD for single cell data. A UMAP embedding plot showing cell types of all 16,101 cells from 18 patients with advanced stage (III/IV) lung adenocarcinoma. Cells were colored according to cell types. B Histogram showing the average CDKN1A expression levels in 18 patients. Based on CDKN1A expression levels, patients were stratified into two distinct groups: high expression (highlighted in red) versus low expression groups (highlighted in blue). C–D Scatterplot showing the Spearman correlations between CDKN1A average expression and enrichment scores of senescence (C), NABA ECM regulators, and PID integrin gene sets (D). Dots were colored according to CDKN1A groups. E Enrichment scores of senescence gene sets between distinct CDKN1A groups in tumor cells (BH-adjusted wilcoxon signed-rank test). F Volcano plot revealing the statistical significance and odds ratios (ORs) for the percentages of cell subpopulation enrichments between CDKN1A high versus low groups (Fisher’s exact test). Point size and color indicated the magnitude of log2 odds ratio. G Dot plot showing the significantly increased cell–cell interactions between distinct CDKN1A expression groups. The color key from blue to red represented the higher communication strength. The dot size represented the significance. Enhanced cellular communications in CDKN1A high expression group were highlighted by red labels. H Histogram showing the average CDKN1A, COL1A1, COL1A2, and NAMPT expression levels in tumor cells between CDKN1A groups (Wilcoxon signed-rank test). I Volcano plot displaying the results of differential activity analysis for transcription factors (TFs) between epithelial cells with high and low expression of CDKN1A. Each point represents a TF. Points are colored based on statistical significance and magnitude of change: red indicates TFs with significantly enhanced activity in the CDKN1A-high group (Wilcoxon rank-sum test, adjusted p-value < 0.05, mean difference > 0), blue indicates TFs with significantly reduced activity (adjusted p-value < 0.05, mean difference < 0), and gray indicates non-significant TFs. J Heatmap depicting z-score normalized transcription factor (TF) activity scores (inferred using the Dorothea package) for top 20 activated TFs (adjusted p-value < 0.05) across samples, grouped by CDKN1Aexpression status (high vs. low) K SpatialFeaturePlot of a representative tissue section from human lung adenocarcinoma samples, showcasing the spatial expression patterns of CDKN1A, NAMPT, SDC1, a pan-tumor epithelial marker (EPCAM), and immune cell markers (PTPRC/CD45for leukocytes, CD3D for T cells)