Fig. 3: Identification and validation of distinct BPH subgroups.
a Principal component analysis (PCA) based on transcriptional and promoter methylation signatures on RNA-seq data. Green denotes subgroup A, and blue denotes subgroup B. b The clinical and biological differences between two BPH subgroups: BPH-A (n = 8) and BPH-B (n = 10) via using two-sided Fisher’s exact test and Wilcoxon signed-rank test. *p-value < 0.05 assessing differences between two BPH subgroups. HTN (hypertension): p-value = 0.588; BMI > 30: p-value = 0.151; TZ (transition zone) volume: p-value = 0.728; Age: p-value = 0.119; Prostate size: p-value = 0.789; Stromal cluster: p-value = 0.011; Immune genes zcores: p-value = 0.633; Immune score: p-value = 0.101; Stromal score: p-value = 0.002. c The validation of BPH subgroups on an independent microarray study GSE101486 with 21 BPH samples via principal component analysis (PCA). K means clustering identified two distinct subgroups based on BPH subgroup signature from panel b. d Clinical and biological differences are shown between two subgroups: BPH-A (n = 9) and BPH-B (n = 12) from GSE101486 study via using two-sided Fisher’s exact test and Wilcoxon signed-rank test. *p-value < 0.05 assessing differences between two BPH subgroups. HTN: p-value = 0.045; BMI > 30: p-value = 0.035; Age: p-value = 1; Prostate size: p-value = 0.395; Stromal cluster: p-value = 0.014. Bottom left represents GSEA plots of significant enrichment of stromal signature in subgroup BPH-A when comparing with subgroup BPH-B from both current and GSE101486 studies. Bottom right showed the correlation of metabolism dysregulation between two subgroups. The x-axis denotes the normalized enrichment scores from current study, and y-axis denotes the normalized enrichment scores from GSE101486 study. Red dots represent the significant signature with FDR < 0.05 in either one of two studies. Examples of metabolism dysregulation are shown. *p-value < 0.05 assessing differences between two BPH subgroups. e The validation of BPH subgroups on an independent study18 with 30 BPH samples via principal component analysis (PCA), based on BPH subgroup signature from panel b. f Hierarchical clustering and heatmap of transcriptional signature between subgroup BPH-A and control samples. g Hierarchical clustering and heatmap of transcriptional signature between subgroup BPH-B and control samples. h The difference of enriched pathways between BPH subgroups when comparing with control samples. Red dots indicate the difference of MSigDB hallmark signatures via GSEA with FDR ≤ 0.05 between two BPH subgroups. The x and y-axes represent the normalized enrichment score of signatures from each BPH subgroup when comparing to control samples.
