Fig. 2: Spatial proteomics profiling of two stromal archetypes in HCC.

a Schematic diagram of morphology-guided LCM of tumor margin samples of HCC (FR+, n = 15; FR‒, n = 15) at TS, FR, LS, TE and LE, followed by proteomic analysis (n = 127). Scale bars: 1 mm. TS tumor-occupying stroma, FR fibrotic ring, LS non-tumor liver stroma, TE tumor edge, LE liver edge. b Violin plot showing the abundance of proteins related to lipid and amino acid metabolism, inflammation, and stress response in TE compared with LE. Heatmap displays the P values of comparisons between TE and LE. Wilcoxon test. c Heatmap of the differentially expressed proteins in the cancer-associated stroma (FR, TS_FR+, TS_FR‒) or non-tumor liver stroma (LS_FR+, LS_FR‒) (P < 0.05). Paired t-test. ECM-related proteins were shown and classified by their ECM category. d Partial Least Squares Discriminant Analysis (PLS-DA) of FR, TS_FR+, TS_FR‒. e Heatmap of the differentially expressed proteins among cancer-associated stroma (FR, TS_FR+, TS_FR‒). f Network of the genesets upregulated in FR, TS_FR+, and TS_FR‒, respectively. g, h H&E (top left) and 3D reconstruction of the stromal architecture in FR+ (g) and FR‒ (h) HCC. Scale bars: 5 mm. i Representative SHG images from FR (left), TS_FR+ (middle), and TS_FR‒ (right), respectively.