Fig. 2: Immune landscape from preneoplasia to invasive lung adenocarcinoma.

a Significantly enriched functional pathways based on the 291 differentially expressed genes by Ingenuity Pathway Analysis (IPA®; Ingenuity Systems) software. Pathways with –log (p-value) > 10 (p-values are obtained from Fisher’s right-tailed exact test) and an absolute z-score > 0.5 are shown. Pathways that were predicted to be inhibited (negative Z scores) in later stages are in blue and pathways that were predicted to be activated (positive Z scores) in later stages are in orange. The heights of the bars indicate the significance of the enrichment (−log (p-value)) and the scales of the orange or blue colors represent the predicted directionality. Fractions of immune cells including CD4+ T cells (b), CD8+ T cells (c), and CD4/CD8 ratio (d) were estimated using TIMER based on the gene expression using nCounter PanCancer Immune Profiling Panel. Error bars indicate 95% confidence intervals and solid point represent mean value in each stage. The difference of cell fraction among different stages was evaluated using two-sided Kruskal–Wallis H test. Data from 38 patients was used including NL (normal lung tissue), AAH (atypical adenomatous hyperplasia), AIS (adenocarcinoma in situ), MIA (minimally invasive adenocarcinoma), and ADC (invasive adenocarcinoma). (Source data is provided as a source data file).