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. 2021 Dec 17;7(51):eabg3750. doi: 10.1126/sciadv.abg3750

Fig. 4. Intratumor heterogeneity in PLCs.

Fig. 4.

(A) Clustered heatmap of tumor clusters’ hallmark pathway average activities. The tumor clusters were grouped into two functional modules. HCC-1.2 represented cluster 2 of HCC-1. TGF, transforming growth factor; TNFA, tumor necrosis factor a; NFKB, nuclear factor kappa B subunit; UV, ultraviolet; IL6, interleukin 6; STAT3, signal transducer and activator of transcription 3; PI3K, phosphatidylinositol 3-kinase; mTOR, mammalian target of rapamycin. (B) Expression profiles of some differential expression genes of the clusters 2/5/6 in HCC-1T. T.2 represented cluster 2 in HCC-1T. (C) Survival curves of two groups of patients in The Cancer Genome Atlas (TCGA) and Liver Cancer Institute (LCI) cohorts to compare the relative malignancy of ST tumor cluster pairs (cluster 2 versus cluster 5 in HCC-1T). These two groups were divided according to which ST tumor cluster the bulk samples were more similar to an expression level. Log-rank test was used to measure the statistical significance of their relative malignancy degrees. (D) Definition of the boundary areas to study the interaction between two neighbor tumor clusters in HCC-1T. The regions with four spots wide along the boundary lines in each cluster were selected, and the spots of stromal clusters were excluded. (E) Bubble heatmap showing the mean interaction strength between the neighbor clusters at the boundaries for ligand-receptor pairs. Dot size indicated the statistical significances by permutation test. *P < 0.05; **P < 0.01; ***P < 0.001. Dot color indicated the mean interaction strength levels. HCC-1T.2 represented cluster 2 in HCC-1T. ns, not significant. (F) Averaged copy number variation (CNV) profiles for each tumor cluster in HCC-1, inferred from spatial transcriptomes. The color of the lines indicated the amplification (red) and deletion (green). The differences between clusters were highlighted by background colors (red, green, and gray), and their detailed chromosome band labels were also presented. HCC-1L.2 represented cluster 2 in HCC-1L.