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Multi-Omics Analyses Detail Metabolic Reprogramming in Lipids, Carnitines, and Use of Glycolytic Intermediates between Prostate Small Cell Neuroendocrine Carcinoma and Prostate Adenocarcinoma

1
West Coast Metabolomics Center, University of California, Davis, CA 95616, USA
2
Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA
3
Department of Medicine, Oregon Health and Science University, Portland, OR 97239, USA
4
Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR 97239, USA
*
Authors to whom correspondence should be addressed.
Metabolites 2019, 9(5), 82; https://doi.org/10.3390/metabo9050082
Received: 16 March 2019 / Revised: 24 April 2019 / Accepted: 24 April 2019 / Published: 26 April 2019
(This article belongs to the Special Issue Mass Spectrometry-Based Metabolomics: Challenges and Applications)
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Abstract

As the most common cancer in men, prostate cancer is molecularly heterogeneous. Contributing to this heterogeneity are the poorly understood metabolic adaptations of the two main types of prostate cancer, i.e., adenocarcinoma and small cell neuroendocrine carcinoma (SCNC), the latter being more aggressive and lethal. Using transcriptomics, untargeted metabolomics and lipidomics profiling on LASCPC-01 (prostate SCNC) and LNCAP (prostate adenocarcinoma) cell lines, we found significant differences in the cellular phenotypes of the two cell lines. Gene set enrichment analysis on the transcriptomics data showed 62 gene sets were upregulated in LASCPC-01, while 112 gene sets were upregulated in LNCAP. ChemRICH analysis on metabolomics and lipidomics data revealed a total of 25 metabolite clusters were significantly different. LASCPC-01 exhibited a higher glycolytic activity and lower levels of triglycerides, while the LNCAP cell line showed increases in one-carbon metabolism as an exit route of glycolytic intermediates and a decrease in carnitine, a mitochondrial lipid transporter. Our findings pinpoint differences in prostate neuroendocrine carcinoma versus prostate adenocarcinoma that could lead to new therapeutic targets in each type. View Full-Text
Keywords: oxygen consumption rate; extracellular acidification rate; hydrophilic interaction liquid chromatography (HILIC); N-Myc oxygen consumption rate; extracellular acidification rate; hydrophilic interaction liquid chromatography (HILIC); N-Myc
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Gao, B.; Lue, H.-W.; Podolak, J.; Fan, S.; Zhang, Y.; Serawat, A.; Alumkal, J.J.; Fiehn, O.; Thomas, G.V. Multi-Omics Analyses Detail Metabolic Reprogramming in Lipids, Carnitines, and Use of Glycolytic Intermediates between Prostate Small Cell Neuroendocrine Carcinoma and Prostate Adenocarcinoma. Metabolites 2019, 9, 82.

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