PMID- 36768152 OWN - NLM STAT- MEDLINE DCOM- 20230214 LR - 20240421 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 3 DP - 2023 Jan 17 TI - Detectable Lipidomes and Metabolomes by Different Plasma Exosome Isolation Methods in Healthy Controls and Patients with Advanced Prostate and Lung Cancer. LID - 10.3390/ijms24031830 [doi] LID - 1830 AB - Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment. Plasma exosomes were isolated from CRPC (n = 10), NSCLC (n = 14), and healthy controls (n = 10) using three different methods: size exclusion chromatography (SEC), lectin binding, and T-cell immunoglobulin domain and mucin domain-containing protein 4 (TIM4) binding. Molecular profiles were determined by mass spectrometry of extracted exosome fractions. Enrichment analysis of uniquely detected molecules was performed for each method with MetaboAnalyst. The exosome enrichment index (EEI) scores methods based on top differential molecules between patient groups. The lipidomic analysis detected 949 lipids using exosomes from SEC, followed by 246 from lectin binding and 226 from TIM4 binding. The detectable metabolites showed SEC identifying 191 while lectin binding and TIM4 binding identified 100 and 107, respectively. When comparing uniquely detected molecules, different methods showed preferential enrichment of different sets of molecules with SEC enriching the greatest diversity. Compared to controls, SEC identified 28 lipids showing significant difference in NSCLC, while only 1 metabolite in NSCLC and 5 metabolites in CRPC were considered statistically significant (FDR < 0.1). Neither lectin-binding- nor TIM4-binding-derived exosome lipids or metabolites demonstrated significant differences between patient groups. We observed the highest EEI from SEC in lipids (NSCLC: 871.33) which was also noted in metabolites. These results support that the size exclusion method of exosome extraction implemented by SBI captures more heterogeneous exosome populations. In contrast, lectin-binding and TIM4-binding methods bind surface glycans or phosphatidylserine moieties of the exosomes. Overall, these findings suggest that specific isolation methods select subpopulations which may significantly impact cancer biomarker discovery. FAU - Soupir, Alex C AU - Soupir AC AUID- ORCID: 0000-0003-1251-9179 AD - Department of Tumor Biology, Moffitt Cancer Center, Tampa, FL 33612, USA. AD - Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Tian, Yijun AU - Tian Y AD - Department of Tumor Biology, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Stewart, Paul A AU - Stewart PA AUID- ORCID: 0000-0003-0882-308X AD - Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Nunez-Lopez, Yury O AU - Nunez-Lopez YO AUID- ORCID: 0000-0003-0382-9124 AD - Advent Health, Translational Research Institute for Metabolism and Diabetes, Orlando, FL 32804, USA. FAU - Manley, Brandon J AU - Manley BJ AUID- ORCID: 0000-0002-7927-1510 AD - Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Pellini, Bruna AU - Pellini B AUID- ORCID: 0000-0003-0898-0202 AD - Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Bloomer, Amanda M AU - Bloomer AM AUID- ORCID: 0000-0002-2737-8631 AD - Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Zhang, Jingsong AU - Zhang J AD - Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Mo, Qianxing AU - Mo Q AUID- ORCID: 0000-0002-0021-7694 AD - Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Marchion, Douglas C AU - Marchion DC AD - Tissue Core, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Liu, Min AU - Liu M AD - Proteomics & Metabolomics Core, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Koomen, John M AU - Koomen JM AD - Department of Molecular Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Siegel, Erin M AU - Siegel EM AUID- ORCID: 0000-0003-1779-2510 AD - Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Wang, Liang AU - Wang L AUID- ORCID: 0000-0002-9364-8572 AD - Department of Tumor Biology, Moffitt Cancer Center, Tampa, FL 33612, USA. LA - eng GR - R01CA212097/NH/NIH HHS/United States GR - P30 CA076292/CA/NCI NIH HHS/United States GR - R01 CA212097/CA/NCI NIH HHS/United States GR - P30-CA076292/NH/NIH HHS/United States PT - Journal Article DEP - 20230117 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Lipids) RN - 0 (Lectins) SB - IM MH - Male MH - Humans MH - *Lung Neoplasms/metabolism MH - *Carcinoma, Non-Small-Cell Lung/metabolism MH - *Exosomes/metabolism MH - Lipidomics MH - Prostate/metabolism MH - *Prostatic Neoplasms, Castration-Resistant/metabolism MH - Metabolome MH - Lipids/analysis MH - Lectins/metabolism PMC - PMC9916336 OTO - NOTNLM OT - cancer multiome OT - circulating lipids OT - circulating metabolites OT - exosome extraction OT - plasma omics COIS- The authors declare no conflict of interest. EDAT- 2023/02/12 06:00 MHDA- 2023/02/15 06:00 PMCR- 2023/01/17 CRDT- 2023/02/11 01:18 PHST- 2022/12/12 00:00 [received] PHST- 2023/01/05 00:00 [revised] PHST- 2023/01/12 00:00 [accepted] PHST- 2023/02/11 01:18 [entrez] PHST- 2023/02/12 06:00 [pubmed] PHST- 2023/02/15 06:00 [medline] PHST- 2023/01/17 00:00 [pmc-release] AID - ijms24031830 [pii] AID - ijms-24-01830 [pii] AID - 10.3390/ijms24031830 [doi] PST - epublish SO - Int J Mol Sci. 2023 Jan 17;24(3):1830. doi: 10.3390/ijms24031830.