Fig. 3: Spatial transcriptome analysis of a patient with GATA3 mutation-positive ductal carcinoma in situ (DCIS) (Patient A).

a Visualization of the Visium results for Patient A. Hematoxylin and eosin staining (left). In total, 2043 spots in the tissue are represented. Morphologically, those cells were classified as cancer cells in situ (405 spots) and noncancer cells (1638 spots). Three cancer cell populations classified via nonhierarchical k-means clustering (k = 9) are shown with different colors (middle panel). Four noncancer spots are similarly shown to represent the gene expression reflecting the microenvironments at the corresponding positions (right panel). b The spots in which GATA3 mutations were detected as transcriptomic tags are colored red. Of the 422 spots morphologically located with cancer cells, a GATA3 mutation read was found for 46 spots. c MA plot presenting differentially expressed genes (DEGs) between spots with and without GATA3 mutations. In total, 1468 DEGs were detected at a false discovery rate of <0.05 (left). The right panel shows a comparison of progesterone receptor (PgR) expression at each spot. Decreased PgR expression was more frequently observed in the spots with GATA3 mutations (P = 0.02901, one-sided t-test). d Results of the enrichment test for the MSigDB v5.1 Hallmark gene set collection (HALLMARK) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways are presented. Each band represents one enriched term or pathway. The level of enrichment is color-coded as the −log 10 p value. As indicated, in the spots with GATA3 mutations, the DEGs were mainly enriched in epithelial-mesenchymal transition (“Gene group A”) and angiogenesis (“Gene group B”). Conversely, in the spots without GATA3 mutations, the DEGs were mainly enriched in tight junctions, estrogen response (“Gene group C”), and MTORC1 signaling. e Violin plots showing the expression of representative genes corresponding to the gene groups of A–C. The expression of the indicated gene was compared between the spots with and without GATA3 mutations in the upper panel. *P < 0.05 (one-sided), n.s.: not significant. The gene expression levels in the tissue are shown in the bottom panel.