Modulation of Plasma Lipidomic Profiles in Metastatic Castration-Resistant Prostate Cancer by Simvastatin

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dc.contributor.authorMak, B.
dc.contributor.authorLin, H.-M.
dc.contributor.authorDuong, T.
dc.contributor.authorMahon, K.L.
dc.contributor.authorJoshua, A.M.
dc.contributor.authorStockler, M.R.
dc.contributor.authorGurney, H.
dc.contributor.authorParnis, F.
dc.contributor.authorZhang, A.
dc.contributor.authorScheinberg, T.
dc.contributor.authorWittert, G.
dc.contributor.authorButler, L.M.
dc.contributor.authorSullivan, D.
dc.contributor.authorHoy, A.J.
dc.contributor.authorMeikle, P.J.
dc.contributor.authorHorvath, L.G.
dc.date.issued2022
dc.description.abstractElevated circulating sphingolipids are associated with shorter overall survival and therapeutic resistance in metastatic castration-resistant prostate cancer (mCRPC), suggesting that perturbations in sphingolipid metabolism promotes prostate cancer growth. This study assessed whether addition of simvastatin to standard treatment for mCRPC can modify a poor prognostic circulating lipidomic profile represented by a validated 3-lipid signature (3LS). Men with mCRPC (n = 27) who were not on a lipid-lowering agent, were given simvastatin for 12 weeks (40 mg orally, once daily) with commencement of standard treatment. Lipidomic profiling was performed on their plasma sampled at baseline and after 12 weeks of treatment. Only 11 men had the poor prognostic 3LS at baseline, of whom five (45%) did not retain the 3LS after simvastatin treatment (expected conversion rate with standard treatment = 19%). At baseline, the plasma profiles of men with the 3LS displayed higher levels (p < 0.05) of sphingolipids (ceramides, hexosylceramides and sphingomyelins) than those of men without the 3LS. These plasma sphingolipids were reduced after statin treatment in men who lost the 3LS (mean decrease: 23–52%, p < 0.05), but not in men with persistent 3LS, and were independent of changes to plasma cholesterol, LDL-C or triacylglycerol. In conclusion, simvastatin in addition to standard treatment can modify the poor prognostic circulating lipidomic profile in mCRPC into a more favourable profile at twice the expected conversion rate.
dc.description.statementofresponsibilityBlossom Mak, Hui-Ming Lin, Thy Duong, Kate L. Mahon, Anthony M. Joshua, Martin R. Stockler, Howard Gurney, Francis Parnis, Alison Zhang, Tahlia Scheinberg, Gary Wittert, Lisa M. Butler, David Sullivan, Andrew J. Hoy, Peter J. Meikle, and Lisa G. Horvath
dc.identifier.citationCancers, 2022; 14(19):1-15
dc.identifier.doi10.3390/cancers14194792
dc.identifier.issn2072-6694
dc.identifier.issn2072-6694
dc.identifier.orcidWittert, G. [0000-0001-6818-6065]
dc.identifier.orcidButler, L.M. [0000-0003-2698-3220]
dc.identifier.urihttps://hdl.handle.net/2440/136770
dc.language.isoen
dc.publisherMDPI AG
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1196225
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2009965
dc.rights© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
dc.source.urihttps://doi.org/10.3390/cancers14194792
dc.subjectceramides; metabolic therapy; lipidomic; prostate cancer; sphingolipids; statins
dc.titleModulation of Plasma Lipidomic Profiles in Metastatic Castration-Resistant Prostate Cancer by Simvastatin
dc.typeJournal article
pubs.publication-statusPublished

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