Fig. 6: Spatial distribution of VEGF signaling during cancer initiation.

a Alluvial plot showing selected VEGFA–NRP1/NRP2/KDR/FLT1 interactions between different initiation stages of epithelial cells and other cell subclusters. b mIHC staining of VEGFA in one patient of diverse initiation stages. Scale bars: 500 μm. c ST feature plots showing the expression of VEGFA in different distributions. Red solid lines circled total epithelium region of N and DN stages; black dotted lines indicated the upper layer of epithelium, mainly composed of differentiated keratinocytes. d Quantitative scores of expression levels of VEGFA in upper and lower layer of the corresponding ST sections. A two-tailed paired Student’s t-test for the P values. *P < 0.05. e Scores of VEGFA-NRP1/NRP2/KDR/FLT1 interactions between the upper layer and lower layer of epithelium in diverse ST sections. Significant mean and significance (P < 0.05) were calculated based on the interaction and the normalized cell matrix achieved by Seurat Normalization. f ST feature plots showing the expression of CD68 in different distributions. Red solid lines circled total epithelium region of N and DN stages; black dotted lines indicated the upper layer of epithelium, mainly composed of differentiated keratinocytes. g mIHC staining of VEGFA, PD-L1, TGFβ1, and PanCK in one patient of diverse initiation stages. Scale bars: 500 μm.