Fig. 4: Transcriptional stratification identifies FH-deficient RCC tumor subsets with distinct biologic features. | Nature Communications

Fig. 4: Transcriptional stratification identifies FH-deficient RCC tumor subsets with distinct biologic features.

From: Comprehensive molecular profiling of FH-deficient renal cell carcinoma identifies molecular subtypes and potential therapeutic targets

Fig. 4

a Heatmap representing ssGSEA scores of MSigDb hallmark gene set for each cluster. b Heatmap of expression level of genes comprised in transcriptional signatures for each cluster. Samples were grouped by cluster. c Box plots depicte the Z-scores of T effector, angiogenesis, stroma, MAPK/ERK, NOTCH, Wnt/β-catenin, proliferation signatures for different clusters (C1-C3). C1, n = 27; C2, n = 23; C3, n = 6. Box plots show median levels (middle line), 25th and 75th percentile (box), 1.5 times the interquartile range (whiskers) as well as outliners (single points). P-values were determined by the two-sided Mann-Whitney test. d Bar chart depicting the proportions of tumors with average CD8 IHC expression ≤50 cells/mm2 and >50 cells/mm2 in different molecular subtypes of FH-deficient RCC. C1 (n = 20), C2 (n = 15), C3 (n = 4). P-value was determined by the two-sided Fisher’s exact test. e Bar chart depicting the proportions of patients with negative (TPS < 1%) or positive (TPS ≥ 1%) PD-L1 expression by IHC in different molecular subtypes of FH-deficient RCC. C1 (n = 27), C2 (n = 20), C3 (n = 6). P-value was determined by the two-sided Pearson’s Chi-squared test with continuity correction. f Box plots depicting the number of CD8+CXCL13+, CD8+ TIGIT+, CD8+PD1+, CD4+TIGIT+, CD4+PD1+ cells/mm2 in different molecular subtypes of FH-deficient RCC. CD8+/PD-1+, CD4+/PD-1+, CD8+/TIGIT+ and CD4+/TIGIT+ markers to depict exhausted CD8+ and CD4+ T cells; while CD8+/CXCL13+ to represent anti-tumor CD8+ T cells. Box plots show median levels (middle line), 25th and 75th percentile (box), 1.5 times the interquartile range (whiskers) as well as outliners (single points). P-values were determined by the two-sided Kruskal-Wallis test. g, h Box plots depicting the ssGSEA scores of CCP score (g) and cancer stemness score (h) in different molecular subtypes of FH-deficient RCC. C1, n = 27; C2, n = 23; C3, n = 6. Box plots show median levels (middle line), 25th and 75th percentile (box), 1.5 times the interquartile range (whiskers), and specific score of each sample (single dots). P-values were determined by the two-sided Kruskal-Wallis test. RCC renal cell carcinoma, ssGSEA single-sample gene set enrichment analysis, IHC immunohistochemistry, TPS tumor proportion score, CCP cell cycle progression. Source data are provided as a Source Data file.

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