Fig. 1: Transcription factor genes are highly enriched nearby PCa risk loci and the 17q12 HNF1B is associated with PCa cell growth and tumor progression. | Nature Communications

Fig. 1: Transcription factor genes are highly enriched nearby PCa risk loci and the 17q12 HNF1B is associated with PCa cell growth and tumor progression.

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

Fig. 1

a Transcription factor genes are more likely to be enriched in PCa susceptibility loci (n = 60669). P value was evaluated by the two-sided Fisher’s exact test. b Circos visualization of enriched transcription factor genes and relevant PCa risk loci. c Phenome-wide association analysis (PheWAS) for an unbiased examination of potential associations between the transcription factor gene enriched PCa risk loci and 2,264 disease endpoints in the FinnGen study (n = 176,899). P values were obtained from the PheWAS study, and the genome-wide significance threshold was defined as P = 5 × 10−8. The y-axis indicates the SNPs of the loci described in b. Note that the 17q12 alleles are prevalent in association with PCa in this PheWAS assessment. d Depletion of HNF1B in V16A through lentivirus-mediated shRNA interference. n = 3 samples; P values based on the order of appearance: 2E–04, 2E–03. e HNF1B knockdown reduces PCa cell proliferation. n = 3 samples; P values HNF1B siRNA1: 5,4E–04, siRNA2: 4,9E–04. f Wound healing assay in the V16A cells infected with lentiviruses expressing shRNAs targeting HNF1B. n = 3 samples; P values HNF1B siRNA1: 2,3E–04, siRNA2: 4,1E–04. g Genome-wide loss-of-function screen in VCaP identified essential genes including HNF1B and ERG for cell survival. Lower scores indicate higher dependency on the gene for cell viability. AR, HOXB13, FOXA1, and MYC are well-known genes driving PCa cell proliferation and survival whereas tumor suppressor PTEN does not favor PCa cell growth and survival. HNF1B is highly expressed in primary prostate tumors (h, n = 34) and metastases (I, n = 112) compared to normal tissues. In (h), P value was assessed by two-sided Mann–Whitney U test. HNF1B expression level is increased in high-grade tumors indicated by higher clinical Grade (j, n = 58) and Gleason scores (k, n = 69). In (i–k), P values were evaluated by Kruskal-Wallis test. In (d–f), n = 3 technical replicates, error bars, mean ± SD, ** P < 0.01, *** P < 0.001, P values were evaluated using the two-tailed Student’s t tests. In h-k, 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). Source data are provided in Source Data file.

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