Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters
1
Department of Internal Medicine, Division of Medical Oncology, University of Kentucky, Lexington, KY 40536, USA
2
Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
3
Department of Neuroscience, University of Kentucky College of Medicine, Lexington, KY 40536, USA
4
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
5
Department of Urology, University of Kentucky, Lexington, KY 40536, USA
6
Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington KY 40536, USA
7
Department of Internal Medicine-Health Services Research, University of Kentucky, Lexington, KY 40536, USA
8
Department of Radiation Medicine, University of Kentucky, Lexington, KY 40536, USA
*
Author to whom correspondence should be addressed.
Academic Editor: José I. López
Cancers 2021, 13(9), 2157; https://doi.org/10.3390/cancers13092157
Received: 23 March 2021
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Revised: 24 April 2021
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Accepted: 28 April 2021
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Published: 29 April 2021
(This article belongs to the Special Issue Urological Cancer 2021)
Simple Summary
High expression levels of glutaminase (GLS1) are reported for several cancers, and correlate with parameters of disease status. GLS1, the rate-limiting enzyme in the glutamine pathway, is involved in DNA/RNA and amino acid synthesis and contributes to other pathways (e.g., TCA cycle). Inhibition of GLS1 has shown anti-tumor activity in both solid tumors and hematological malignancies. The CB-839 agent, a novel GLS1 inhibitor, has been under investigation clinically. GLS1 expression by immunohistochemical (IHC) staining in prostate has not been definitively demonstrated. We present a retrospective study evaluating GLS1 expression utilizing The Cancer Genome Atlas (TCGA) RNA-Seq data and by IHC in formalin-fixed paraffin embedded radical prostatectomy samples. The study showed a significant difference in GLS1 levels between cancer and non-cancer, but fell short as a prognostic marker. As the study cohort was skewed to less aggressive localized prostate cancer, we support further studies that incorporate high-risk and very high-risk localized and metastatic prostate cancers.
High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer.
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Keywords:
glutaminase; immunohistochemistry; in situ methods; prostate; prognosis
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MDPI and ACS Style
Myint, Z.W.; Sun, R.C.; Hensley, P.J.; James, A.C.; Wang, P.; Strup, S.E.; McDonald, R.J.; Yan, D.; St. Clair, W.H.; Allison, D.B. Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters. Cancers 2021, 13, 2157. https://doi.org/10.3390/cancers13092157
AMA Style
Myint ZW, Sun RC, Hensley PJ, James AC, Wang P, Strup SE, McDonald RJ, Yan D, St. Clair WH, Allison DB. Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters. Cancers. 2021; 13(9):2157. https://doi.org/10.3390/cancers13092157
Chicago/Turabian StyleMyint, Zin W., Ramon C. Sun, Patrick J. Hensley, Andrew C. James, Peng Wang, Stephen E. Strup, Robert J. McDonald, Donglin Yan, William H. St. Clair, and Derek B. Allison. 2021. "Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters" Cancers 13, no. 9: 2157. https://doi.org/10.3390/cancers13092157
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