Exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted LC-MS based metabolomics kit to discriminate leptomeningeal metastasis
Abstract Background Leptomeningeal metastasis (LM) is a devastating complication of cancer that is difficult to treat. Thus, early diagnosis is essential for LM patients. However, cerebrospinal fluid (CSF) cytology has low sensitivity, and imaging approaches are ineffective. We explored targeted CSF...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s40170-024-00367-x |
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| author | Soojin Jang Ho-Shin Gwak Kyue-Yim Lee Jun Hwa Lee Kyung-Hee Kim Jong Heon Kim Jong Bae Park Sang Hoon Shin Heon Yoo Yun-Sik Dho Kyu-Chang Wang Byong Chul Yoo |
| author_facet | Soojin Jang Ho-Shin Gwak Kyue-Yim Lee Jun Hwa Lee Kyung-Hee Kim Jong Heon Kim Jong Bae Park Sang Hoon Shin Heon Yoo Yun-Sik Dho Kyu-Chang Wang Byong Chul Yoo |
| author_sort | Soojin Jang |
| collection | DOAJ |
| description | Abstract Background Leptomeningeal metastasis (LM) is a devastating complication of cancer that is difficult to treat. Thus, early diagnosis is essential for LM patients. However, cerebrospinal fluid (CSF) cytology has low sensitivity, and imaging approaches are ineffective. We explored targeted CSF metabolic profiling to discriminate among LM and other conditions affecting the central nervous system (CNS). Methods We quantitatively measured amino acids, biogenic amines, hexoses, acylcarnitines (AC), cholesteryl esters (CE), glycerides, phosphatidylcholines (PC), lysophosphatidylcholines (LPC), sphingomyelins (SM), and ceramides (Cer) in 117 CSF samples from various groups of healthy controls (HC, n = 10), patients with LM (LM, n = 47), parenchymal brain tumor (PBT, n = 45), and inflammatory disease (ID, n = 13) with internal standards using the Absolute IDQ- p400® targeted mass spectrometry kit. Metabolites detected in > 90% of samples or showing a difference in proportional level between groups ≥ 75% were used in logistic regression models when there was no single metabolite with AUC = 1 for the groups of comparison. Results PC and SM had higher levels in LM than in PBT or HC, whereas LPC had lower level in PBT than the other groups. Glycerides and Cer levels were higher in PBT and LM than in HC. Long-chain AC level in PBT was lower than in LM or HC. A regression model including Ala, PC (42:7), PC (30:3), PC (37:0), and Tyr achieved complete discrimination (AUC = 1.0) between LM and HC. In comparison of PBT and HC, twenty-six individual metabolites allowed complete discrimination between two groups, and between ID and HC fourty-six individual lipid metabolites allowed complete discrimination. Twenty-one individual metabolites (18 ACs and 3 PCs) allowed complete discrimination between LM and PBT. Conclusions Using a commercial targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics kit, we were able to differentiate LM from HC and PBT. Most of the discriminative metabolites among different diseases were lipid metabolites, for which their CNS distribution and quantification in different cell types are largely unknown, whereas amino acids, biogenic amines, and hexoses failed to show significant differences. Future validation studies with larger, controlled cohorts should be performed, and hopefully, the kit may expand its metabolite coverage for unique cancer cell glucose metabolism. |
| format | Article |
| id | doaj-art-f8f5b8296ad440ed9aace97eab512cc3 |
| institution | Kabale University |
| issn | 2049-3002 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Cancer & Metabolism |
| spelling | doaj-art-f8f5b8296ad440ed9aace97eab512cc32025-01-26T12:49:03ZengBMCCancer & Metabolism2049-30022025-01-0113111410.1186/s40170-024-00367-xExploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted LC-MS based metabolomics kit to discriminate leptomeningeal metastasisSoojin Jang0Ho-Shin Gwak1Kyue-Yim Lee2Jun Hwa Lee3Kyung-Hee Kim4Jong Heon Kim5Jong Bae Park6Sang Hoon Shin7Heon Yoo8Yun-Sik Dho9Kyu-Chang Wang10Byong Chul Yoo11Department of Neurosurgery, College of Medicine, Seoul National UniversityDepartment of Cancer Control, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer CenterDepartment of Cancer Control, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer CenterBiomarker Branch, and Cancer Diagnostics Branch, Division of Cancer Biology, Research Institute, National Cancer CenterBiomarker Branch, and Cancer Diagnostics Branch, Division of Cancer Biology, Research Institute, National Cancer CenterDepartment of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer CenterDepartment of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer CenterNeuro-oncology Clinic, National Cancer CenterNeuro-oncology Clinic, National Cancer CenterNeuro-oncology Clinic, National Cancer CenterNeuro-oncology Clinic, National Cancer CenterInnoBation BioAbstract Background Leptomeningeal metastasis (LM) is a devastating complication of cancer that is difficult to treat. Thus, early diagnosis is essential for LM patients. However, cerebrospinal fluid (CSF) cytology has low sensitivity, and imaging approaches are ineffective. We explored targeted CSF metabolic profiling to discriminate among LM and other conditions affecting the central nervous system (CNS). Methods We quantitatively measured amino acids, biogenic amines, hexoses, acylcarnitines (AC), cholesteryl esters (CE), glycerides, phosphatidylcholines (PC), lysophosphatidylcholines (LPC), sphingomyelins (SM), and ceramides (Cer) in 117 CSF samples from various groups of healthy controls (HC, n = 10), patients with LM (LM, n = 47), parenchymal brain tumor (PBT, n = 45), and inflammatory disease (ID, n = 13) with internal standards using the Absolute IDQ- p400® targeted mass spectrometry kit. Metabolites detected in > 90% of samples or showing a difference in proportional level between groups ≥ 75% were used in logistic regression models when there was no single metabolite with AUC = 1 for the groups of comparison. Results PC and SM had higher levels in LM than in PBT or HC, whereas LPC had lower level in PBT than the other groups. Glycerides and Cer levels were higher in PBT and LM than in HC. Long-chain AC level in PBT was lower than in LM or HC. A regression model including Ala, PC (42:7), PC (30:3), PC (37:0), and Tyr achieved complete discrimination (AUC = 1.0) between LM and HC. In comparison of PBT and HC, twenty-six individual metabolites allowed complete discrimination between two groups, and between ID and HC fourty-six individual lipid metabolites allowed complete discrimination. Twenty-one individual metabolites (18 ACs and 3 PCs) allowed complete discrimination between LM and PBT. Conclusions Using a commercial targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics kit, we were able to differentiate LM from HC and PBT. Most of the discriminative metabolites among different diseases were lipid metabolites, for which their CNS distribution and quantification in different cell types are largely unknown, whereas amino acids, biogenic amines, and hexoses failed to show significant differences. Future validation studies with larger, controlled cohorts should be performed, and hopefully, the kit may expand its metabolite coverage for unique cancer cell glucose metabolism.https://doi.org/10.1186/s40170-024-00367-xCerebrospinal fluidMetabolomeLeptomeningeal metastasisProfileDiagnosis |
| spellingShingle | Soojin Jang Ho-Shin Gwak Kyue-Yim Lee Jun Hwa Lee Kyung-Hee Kim Jong Heon Kim Jong Bae Park Sang Hoon Shin Heon Yoo Yun-Sik Dho Kyu-Chang Wang Byong Chul Yoo Exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted LC-MS based metabolomics kit to discriminate leptomeningeal metastasis Cancer & Metabolism Cerebrospinal fluid Metabolome Leptomeningeal metastasis Profile Diagnosis |
| title | Exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted LC-MS based metabolomics kit to discriminate leptomeningeal metastasis |
| title_full | Exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted LC-MS based metabolomics kit to discriminate leptomeningeal metastasis |
| title_fullStr | Exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted LC-MS based metabolomics kit to discriminate leptomeningeal metastasis |
| title_full_unstemmed | Exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted LC-MS based metabolomics kit to discriminate leptomeningeal metastasis |
| title_short | Exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted LC-MS based metabolomics kit to discriminate leptomeningeal metastasis |
| title_sort | exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted lc ms based metabolomics kit to discriminate leptomeningeal metastasis |
| topic | Cerebrospinal fluid Metabolome Leptomeningeal metastasis Profile Diagnosis |
| url | https://doi.org/10.1186/s40170-024-00367-x |
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