Fig. 4: HNF1B gene signatures correlate with PCa progression in the clinical setting. | Nature Communications

Fig. 4: HNF1B gene signatures correlate with PCa progression in the clinical setting.

From: Extensive germline-somatic interplay contributes to prostate cancer progression through HNF1B co-option of TMPRSS2-ERG

Fig. 4

a Depletion of HNF1B in VCaP cells treated with DHT 100 nM 72hrs. n = 3 technical replicates, error bars, mean ± SD, ** P < 0.01; two-tailed Student’s t test. n = 3 samples; P values based on the order of appearance: 2,3E–03, 1,4E–03. b Heatmap of HNF1B regulated genes measured by RNA-seq (p < 0.05). P values were evaluated by the Wald test and not adjusted for multiple comparisons. c Top-ranked GSEA enriched pathways associated with genes upregulated and downregulated by HNF1B, respectively. Categories were ranked by Normalized Enrichment Score (NES). d GSEA enrichment plots displaying enrichment of cell-cycle related pathways among HNF1B upregulated genes. e, f Cell-cycle gene signature based on z-score sum of the 33-cell cycle relevant genes differentially regulated by HNF1B showing strong positive correlations with cell cycle progression (CCP) score in the TCGA (n = 493) and SU2C-PCF (n = 266) cohorts, respectively. g Pearson correlation test displays significant positive linear correlation of HNF1B knock-down signature with CCP score in the TCGA cohort (n = 493). In e–g, P values were assessed by the two-sided Pearson’s product-moment correlation test. Higher HNF1B cell cycle signature scores are associated with tumor development and progression to metastasis (h, n = 108), (i, n = 150), (j, n = 122), higher Gleason score (k, n = 139), lymph node-positive PCa (i, n = 425), and higher tumor stages (m, n = 491); two-sided Mann–Whitney U test or Kruskal-Wallis test. The interquartile range (IQR) is depicted by the box with the median represented by the center line. Whiskers maximally extend to 1.5 × IQR (with outliers shown). Kaplan-Meier curves depicting the associations between overall survival (n, n = 71), biochemical relapse (o, n = 492), or metastasis (p, n = 493) of PCa patients and the HNF1B cell cycle signature scores in PCa patients; log-rank test. q Differentially expressed genes that are significantly co-expressed with HNF1B are more likely to be co-expressed with TMPRSS2-ERG in TCGA cohort (n = 498); two-sided Fisher’s exact test. r A 25 gene co-expression signature with HNF1B displayed a similar expression pattern as ERG in DKFZ cohort (n = 118). Source data are provided in Source Data file.

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