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Fig. 3 | Genome Medicine

Fig. 3

From: Human liver single nucleus and single cell RNA sequencing identify a hepatocellular carcinoma-associated cell-type affecting survival

Fig. 3

The HCC-enriched Prol cell-type associates with overall survival (OS) and progression free interval (PFI) in TCGA and with OS in LCI. Increased Prol cell-type proportion estimates are associated with poor survival outcomes in TCGA and LCI. ac Kaplan-Meier survival curves for (a) overall survival (OS) and (b) progression free interval (PFI) in TCGA and (c) OS in LCI show worse survival outcomes for patients with high liver Prol cell-type frequency estimates. Patients with Prol frequency (freq.) estimates above and below the median were classified into high and low groups, respectively. The “+” signs on the line indicate right censoring of the event. The hazard ratios (HR) and FDR adjusted p-values were calculated from a Cox proportional hazards regression adjusting for age, sex, and for TCGA, race. df Association of the Prol cell-type with poor survival outcomes is highlighted by the HR values for cell-type marker genes calculated from a Cox proportional hazards regression of their expression in TCGA and LCI. Survival tests were performed for (d) OS and (e) PFI in TCGA and (f) OS in LCI. Each dot indicates a gene, with its HR on the x-axis and its cell-type on the y-axis. gl Module scores of survival-decreasing genes in the single-cell level data are significantly higher in cells/nuclei from the Prol cell-type. Survival-decreasing genes were derived from genome-wide Cox proportional hazards regression analyses of all genes for the indicated event and cohort and taking the genes with FDR-adjusted p-values less than 0.05 and HR values greater than 1.0 into the module score analyses in (g–l). gi UMAP plots show cells/nuclei colored by (g) TCGA OS score, (h) TCGA PFI score, and (i) LCI OS scores. j, l Bar plots of survival-decreasing module scores for (j) TCGA OS, (k) TCGA PFI, and (l) LCI OS separated by the cell-type. gl Asterisks denote a significant difference in survival-decreasing gene scores between Prol and non-Prol cells/nuclei as assessed by a Wilcoxon test. Significance levels for p-values: *p < 0.05, **p < 0.005, ***p < 0.0005

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