C-MYC, HIF-1α, ERG, TKT, and GSTP1: an Axis in Prostate Cancer?

Abstract

To analyze putative biomarkers for prostate cancer (PCA) characterization, the second leading cause of cancer-associated mortality in men. Quantification of the expression level of c-myc and HIF-1α was performed in 72 prostate cancer specimens. A cohort of 497 prostate cancer patients from The Cancer Genome Atlas (TCGA) database was further analyzed, in order to test our hypothesis. We found that high c-myc level was significantly associated with HIF-1α elevated expression (p = 0.008) in our 72 samples. Statistical analysis of 497 TCGA prostate cancer specimens confirmed the strong association (p = 0.0005) of c-myc and HIF-1α expression levels, as we found in our series. Moreover, we found high c-myc levels significantly associated with low Glutatione S-transferase P1 (GSTP1) expression (p = 0.01), with high Transketolase (TKT) expression (p < 0.0001). High TKT levels were found in TCGA samples with low GSTP1 mRNA (p < 0.0001), as shown for c-myc, and with ERG increased expression (p = 0.02). Finally, samples with low GSTP1 expression displayed higher ERG mRNA levels than samples with high GSTP1 score (p < 0.0001), as above shown for c-myc. Our study emphasizes the notion of a potential value of HIF-1α and c-myc as putative biomarkers in prostate cancer; moreover TCGA data analysis showed a putative crosstalk between c-myc, HIF-1α, ERG, TKT, and GSTP1, suggesting a potential use of this axis in prostate cancer.

• Authors: L Boldrini, R Bartoletti, M Giordano, F Manassero, C Selli, M Panichi, L Galli, F Farci, P Faviana
• Journal: Pathology oncology research : POR (Pathol Oncol Res) Vol. 25 Issue 4 Pg. 1423-1429 (Oct 2019) ISSN: 1532-2807 [Electronic] Switzerland
• PMID: 30357756 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• ERG protein, human
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• MYC protein, human
• Proto-Oncogene Proteins c-myc
• Transcriptional Regulator ERG
• Transketolase
• GSTP1 protein, human
• Glutathione S-Transferase pi

Topics

• Aged
• Biomarkers, Tumor (genetics)
• Cohort Studies
• Follow-Up Studies
• Glutathione S-Transferase pi (genetics)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics)
• Male
• Middle Aged
• Prognosis
• Prostatic Neoplasms (genetics, pathology)
• Proto-Oncogene Proteins c-myc (genetics)
• Transcriptional Regulator ERG (genetics)
• Transketolase (genetics)