Fig. 6: Transcriptome patterns in early and advanced lung adenocarcinoma.

a Expression patterns of DEGs between AIS Noguchi type A and B in RNA-seq data. b GO terms enriched in the DEGs in (a). c Expression patterns of DEGs between AIS and MIA/Lepidic-Ad cases in RNA-seq data. d GO terms enriched in the DEGs in (c). e Spatial transcriptome analysis Visium for three representative cases (TSU-20, TSU-21, and TSU-33). Expression patterns of marker genes for well-differentiated tumor cells (NAPSA) and AMs (MARCO) are represented. f Enrichment scores of transcriptome signature genes in the corresponding histological types in Visium data. g Multiplexed fluorescence immunostaining (PhenoCycler) of serial sections of spatial transcriptome data for case TSU-21. Protein expression patterns of representative cell-type markers for the entire region and three regions-of-interests: (1) a macrophage-rich region, (2) a region with lymphocyte infiltration, and (3) a region nearby fibrotic foci characteristic to Noguchi type B tumors. Each antibody was used as a cell-type marker: Pan-cytokeratin, epithelial cells; CD19, B cells; CD4, T cells; CD68, macrophages; and α-SMA/ACTA2, myofibroblasts. h Spatial expression patterns of tumor cell markers in Visium data. i In situ gene expression profiling Xenium for case TSU-21. Clusters are represented in the spatial plot and the UMAP plot in the left and right panels, respectively. The statistics of Xenium data are shown in the margin of the spatial plot. The cell-type annotation is shown in the margin of the UMAP plot. j Xenium spatial expression pattern of an alveolar macrophage marker MARCO (left). Patterns of several macrophage markers in local regions (middle and right). Each dot represents a detected RNA molecule.