Fig. 5: hUSI identifies prognosis-related senescent tumor cells in melanoma.
a, tSNE plot showing the distribution of seven cell types identified within the melanoma dataset (GSE72056). b, The UMAP displays the distribution of hUSI value of each cell in the melanoma dataset. c, Violin plot compares hUSI levels between untreated and treated groups in immune therapy (two-tailed Wilcoxon test). The box in the boxplot represents the IQR, with its lower and upper edges indicating the 25th and 75th percentiles, respectively. The medium value (50th percentile) is shown within the box, and the whiskers extend to the minimum and maximum values within 1.5 times the IQR of the quartiles. ***P < 1 × 10−3. The exact P values are reported in Source Data for Fig. 5. d, The proportions of three tumor senescence subpopulations of untreated and treated groups in immune therapy. e, Senescence trajectory of melanoma tumor cells in PHATE space. f, Increased expression levels of aging-related marker genes CDKN1A and SERPINE along the trajectory in e and in different senescence subpopulations. g, Different GO terms (biological process (BP)) characterize Cycling, Transitional and Senescent subpopulations, with replication-associated terms enriched by the Cycling subpopulation and immunity activation-related terms enriched by the Senescent subpopulation (the hypergeometric test with Benjamini–Hochberg correction). The exact FDR-corrected P values are reported in Source Data for Fig. 5. h, Heatmap of Spearman correlation coefficient between the abundance of the three subpopulations and that of 22 immune cell types. i, Survival curves of patients with melanoma with low or high proportion of Senescent subpopulation in the TCGA-SKCM cohort (log-rank test). j, Dot plot showing the interaction strength of three tumor subpopulations and six cell types in the TME. k, Dot plot of communication probabilities for signaling pathways presenting in the Senescent subpopulation while absent in the Cycling subpopulation (permutation test, n = 100 iterations). l, Chord plots showing that Macro and CAFs interact with Transitional and Senescent subpopulations by the TGFβ signaling pathway. m, Violin plot showing the expression levels of four receptors specifically expressed in the Senescent subpopulation. n, Survival curves of patients with melanoma with low or high enrichment score of TGFBR2, ACVR1, ALCAM and CCR10 in the TCGA-SKCM cohort (log-rank test). tSNE, t-distributed stochastic neighbor embedding.
