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Integrated Pharmacogenetic Signature for the Prediction of Prostatic Neoplasms in Men With Metabolic Disorders

MARIA PAGONI, VASILEIOS L. ZOGOPOULOS, STAVROS KONTOGIANNIS, ANNIA TSOLAKOU, VASSILIOS ZOUMPOURLIS, GEORGE TH. TSANGARIS, ELEFTHERIOS FOKAEFS, IOANNIS MICHALOPOULOS, ARISTIDIS M. TSATSAKIS and NIKOLAOS DRAKOULIS
Cancer Genomics & Proteomics March 2025, 22 (2) 285-305; DOI: https://doi.org/10.21873/cgp.20502

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Figures

  • Figure 1.
    Figure 1.

    Summary of the steroid hormone pathway indicating the production of testosterone hydroxylated metabolites through the enzymatic activity of CYP450s involved in the synthesis and the metabolism of testosterone in humans. Red arrows: CYP3A4; Blue Arrow: CYP2B6; 2C9, 2C19, 3A4; Brown Arrow: CYP19A1 (aromatase).

  • Figure 2.
    Figure 2.

    Ring charts of metabolic profiles in: (a) Benign prostatic hyperplasia (BPH) subjects; (b) BPH in prostate cancer (PCa) subjects; (c) PCa*. The asterisk means that BPH in PCa subjects is excluded.

  • Figure 3.
    Figure 3.

    Comparative health records of patients with prostatic neoplasia. The bar chart illustrates the percentage of Cohort A patients with the registered comorbidities per subgroup of neoplastic disease in examination. Colors represent each subgroup; blue: only benign hyperplasia (BPH) individuals, red: BPH in prostate cancer (PCa) individuals, green: PCa individuals without previous BPH status. The prevalence of hypertension in patients stratified by subgroup of neoplastic disease is observed.

  • Figure 4.
    Figure 4.

    Most frequent ADMET categories observed in the 33 drugs of cohort A (Greek cohort). The relative frequency of each category is displayed on the vertical axis, while the ADMET category name is shown on the horizontal axis.

  • Figure 5.
    Figure 5.
    Figure 5.

    (a) Over-representation analysis (ORA) based on the hypergeometric distribution showing the significantly enriched biological entities that involve the CYP metabolic enzyme targeted by miRNAs as they were identified by the use of the miRabel prediction tool. The heatmap shows that the enriched “prostate cancer entity” term has a functional significance on the CYP3A4 gene, through its epigenetic regulation by hsa-miR-200c-3p; (b) Interactive visualization of maximum-coverage analysis based on miRPathDB 2.0 tool, indicating that numerous miRNAs can target a specific gene of interest. X and Y axes show the increasing number of miRNAs and the number of covered target genes, in this case CYP3A4, which is directly regulated by hsa-miR-27b-3p. This result was further confirmed by miRTarBase.

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Integrated Pharmacogenetic Signature for the Prediction of Prostatic Neoplasms in Men With Metabolic Disorders
MARIA PAGONI, VASILEIOS L. ZOGOPOULOS, STAVROS KONTOGIANNIS, ANNIA TSOLAKOU, VASSILIOS ZOUMPOURLIS, GEORGE TH. TSANGARIS, ELEFTHERIOS FOKAEFS, IOANNIS MICHALOPOULOS, ARISTIDIS M. TSATSAKIS, NIKOLAOS DRAKOULIS
Cancer Genomics & Proteomics Mar 2025, 22 (2) 285-305; DOI: 10.21873/cgp.20502
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