Supplementary Data from TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup
Year: 2023
Type: supplementary-materials
Abstract: Supplement Materials and Methods and Figures S1-S6 Supplement Figure 1: Taylor et al. (2010) data indicate that concurrent TOP2A and EZH2 expression identify primary PCa patients with a more aggressive disease. Supplement Figure 2: GSEA for oncogenic signatures in primary human PCa revealed statistically significant overlapping for gene signatures involving VEGF and E2F1 signaling from the TCGA (2015) and Taylor et al. (2010) datasets. (P < 0.05 and FDR < 0.15; Supplement Table 3). Supplement Figure 3: Genes that have been demonstrated to be up-regulated in indolent primary PCa are down regulated in TCGA (2015) patients with concurrent up-regulation of TOP2A and EZH2 (TOP2A+/EZH2+) (Mann-Whitney; * P < 0.05; *** P < 0.001). Supplement Figure 4: Concurrent high TOP2A and EZH2 expression in primary prostatic tumors (TOP2A+/EZH2+) is not associated to a shorter time to biochemical recurrence when compared to TOP2A-/EZH2- patients included in the (A) Mayo Clinic Validation study, (B) Thomas Jefferson University dataset or the (C) Johns Hopkins University post-RP dataset. Supplement Figure 5: (A) Combination therapy induces loss of clonogenicity specific to dKO cells (top: representative experiment; unpaired t test; ** P < 0.01, triplicate, mean {plus minus}SEM). (B) Cell cycle analysis indicates that combination therapy targeting both EZH2 (GSK126 or EPZ6438, 5 μM) and TOP2A (Etoposide, 1 μM) induces G2M arrest in both sKO and dKO cell lines but results in a significant increase in apoptosis as indicated by SubG1 accumulation only in dKO (unpaired t test; ** P < 0.01, triplicate, mean {plus minus}SEM). Supplement Figure 6: TOP2A and EZH2 co-expression can select for metastatic disease progression and shorter regression-free survival in the TCGA's (A) Clear Renal Cell Carcinoma and the (B) Papillary Kidney Carcinoma datasets. (Abbreviations: no distant metastasis, M0; distant metastasis, M1)
Authors: David P. Labbé, Christopher J. Sweeney, Myles Brown, Phillip Galbo, Spencer Rosario, Kristine M. Wadosky, Sheng-Yu Ku, Martin Sjöström, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, R. Jeffrey Karnes, Edward M. Schaeffer, Robert B. Jenkins, Robert B. Den, Ashley E. Ross, Michaela Bowden, Ying Huang, Kathryn P. Gray, Felix Y. Feng, Daniel E. Spratt, David W. Goodrich, Kevin H. Eng, Leigh Ellis
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4361922005