Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Integrative Metabolomic Analysis of Serum and Selected Serum Exosomal microRNA in Metastatic Castration-Resistant Prostate Cancer

Version 1 : Received: 18 January 2024 / Approved: 18 January 2024 / Online: 19 January 2024 (04:57:31 CET)

A peer-reviewed article of this Preprint also exists.

Evin, D.; Evinová, A.; Baranovičová, E.; Šarlinová, M.; Jurečeková, J.; Kaplán, P.; Poláček, H.; Halašová, E.; Dušenka, R.; Briš, L.; Brožová, M.K.; Sivoňová, M.K. Integrative Metabolomic Analysis of Serum and Selected Serum Exosomal microRNA in Metastatic Castration-Resistant Prostate Cancer. Int. J. Mol. Sci. 2024, 25, 2630. Evin, D.; Evinová, A.; Baranovičová, E.; Šarlinová, M.; Jurečeková, J.; Kaplán, P.; Poláček, H.; Halašová, E.; Dušenka, R.; Briš, L.; Brožová, M.K.; Sivoňová, M.K. Integrative Metabolomic Analysis of Serum and Selected Serum Exosomal microRNA in Metastatic Castration-Resistant Prostate Cancer. Int. J. Mol. Sci. 2024, 25, 2630.

Abstract

Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH). Blood serum samples from mCRPC patients (n=51) and BPH patients (n=48) underwent metabolome analysis through 1H-NMR spectroscopy. The expression levels of serum exosomal miRs in mCRPC and BPH patients were evaluated using quantitative real-time polymerase chain reaction (qRT‒PCR). The 1H-NMR metabolomics analysis revealed significant alterations in lactate, acetate, citrate, 3-hydroxybutyrate, and branched-chain amino acids (BCAAs, including valine, leucine, and isoleucine) in mCRPC patients compared to BPH patients. MiR-15a, miR-16, miR-19a-3p, and miR-21 exhibited a down-regulation of more than twofold in the mCRPC group. Significant correlations were predominantly observed between lactate, citrate, acetate, and miR-15a, miR-16, miR-19a-3p, and miR-21. The importance of integrating metabolome analysis of serum with selected serum exosomal miRs in mCRPC patients has been confirmed, suggesting their potential utility as clinical diagnostic markers.

Keywords

metastatic castration-resistant prostate cancer; microRNA; 1H-NMR metabolomics

Subject

Medicine and Pharmacology, Urology and Nephrology

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