Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis

Abstract Background Multiple myeloma (MM) is the most aggressive and prevalent primary malignant tumor within the blood system, and can be classified into grades RISS-I, II, and III. High-grade tumors are associated with decreased survival rates and increased recurrence rates. To better understand m...

Full description

Saved in:
Bibliographic Details
Main Authors: Xiaoxue Wang, Longhao Cheng, Aijun Liu, Lihong Liu, Lili Gong, Guolin Shen
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-024-05848-7
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1823861629850222592
author Xiaoxue Wang
Longhao Cheng
Aijun Liu
Lihong Liu
Lili Gong
Guolin Shen
author_facet Xiaoxue Wang
Longhao Cheng
Aijun Liu
Lihong Liu
Lili Gong
Guolin Shen
author_sort Xiaoxue Wang
collection DOAJ
description Abstract Background Multiple myeloma (MM) is the most aggressive and prevalent primary malignant tumor within the blood system, and can be classified into grades RISS-I, II, and III. High-grade tumors are associated with decreased survival rates and increased recurrence rates. To better understand metabolic disorders and expand the potential targets for MM, we conducted large-scale untargeted metabolomics on plasma samples from MM patients and healthy controls (HC). Methods Our study included 33 HC, 38 newly diagnosed MM patients (NDMM) categorized into three RISS grades (grade I: n = 5; grade II: n = 19; grade III: n = 8), and 92 MM patients post-targeted therapy with bortezomib-based regimens. Simultaneously, MM cell lines were employed for validation studies. Metabolites were analyzed and identified using ultra high liquid chromatography coupled with Q Orbitrap mass spectrometry (UPLC-HRMS), followed by verification through a self-built database. Results Compared with HC participants, a total of 70 metabolites were identified as undergoing significant changes in NDMM. These metabolites were significantly enriched in citrate cycle, choline metabolism, glycerophospholipid metabolism, and sphingolipid metabolism, etc. Notably, a panel of circulating plasma metabolite biomarkers, including lactic acid and leucine, has emerged not only as diagnostic indicators but also as valuable tools for tumor surveillance, aiding in the assessment of disease stage and prognostic evaluation. Moreover, 14 differential metabolites were identified in both MM cell lines and MM patients. Among these, intracellular levels of lactate and leucine significantly decreased in vitro, aligning with the plasma results. Conclusion Our findings on key metabolites and metabolic pathways provide novel insights into the exploration of diagnostic and therapeutic targets for MM. A prospective study is essential to validate these discoveries for future MM patient care.
format Article
id doaj-art-37bff4abe4db48619b79f46b0d4f19bd
institution Kabale University
issn 1479-5876
language English
publishDate 2025-02-01
publisher BMC
record_format Article
series Journal of Translational Medicine
spelling doaj-art-37bff4abe4db48619b79f46b0d4f19bd2025-02-09T12:52:33ZengBMCJournal of Translational Medicine1479-58762025-02-0123111310.1186/s12967-024-05848-7Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosisXiaoxue Wang0Longhao Cheng1Aijun Liu2Lihong Liu3Lili Gong4Guolin Shen5Department of Pharmacy, China-Japan Friendship HospitalInstitute of Clinical Medical Sciences, State Key Laboratory of Respiratory Health and Multimorbidity, China-Japan Friendship Hospital, Capital Medical UniversityDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical UniversityDepartment of Pharmacy, China-Japan Friendship HospitalInstitute of Clinical Medical Sciences, State Key Laboratory of Respiratory Health and Multimorbidity, China-Japan Friendship Hospital, Capital Medical UniversityInstitute of Chemicals Safety, Chinese Academy of Inspection and QuarantineAbstract Background Multiple myeloma (MM) is the most aggressive and prevalent primary malignant tumor within the blood system, and can be classified into grades RISS-I, II, and III. High-grade tumors are associated with decreased survival rates and increased recurrence rates. To better understand metabolic disorders and expand the potential targets for MM, we conducted large-scale untargeted metabolomics on plasma samples from MM patients and healthy controls (HC). Methods Our study included 33 HC, 38 newly diagnosed MM patients (NDMM) categorized into three RISS grades (grade I: n = 5; grade II: n = 19; grade III: n = 8), and 92 MM patients post-targeted therapy with bortezomib-based regimens. Simultaneously, MM cell lines were employed for validation studies. Metabolites were analyzed and identified using ultra high liquid chromatography coupled with Q Orbitrap mass spectrometry (UPLC-HRMS), followed by verification through a self-built database. Results Compared with HC participants, a total of 70 metabolites were identified as undergoing significant changes in NDMM. These metabolites were significantly enriched in citrate cycle, choline metabolism, glycerophospholipid metabolism, and sphingolipid metabolism, etc. Notably, a panel of circulating plasma metabolite biomarkers, including lactic acid and leucine, has emerged not only as diagnostic indicators but also as valuable tools for tumor surveillance, aiding in the assessment of disease stage and prognostic evaluation. Moreover, 14 differential metabolites were identified in both MM cell lines and MM patients. Among these, intracellular levels of lactate and leucine significantly decreased in vitro, aligning with the plasma results. Conclusion Our findings on key metabolites and metabolic pathways provide novel insights into the exploration of diagnostic and therapeutic targets for MM. A prospective study is essential to validate these discoveries for future MM patient care.https://doi.org/10.1186/s12967-024-05848-7Multiple myelomaBiomarkersMetabolomicsPeripheral plasmaMetabolic pathways
spellingShingle Xiaoxue Wang
Longhao Cheng
Aijun Liu
Lihong Liu
Lili Gong
Guolin Shen
Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis
Journal of Translational Medicine
Multiple myeloma
Biomarkers
Metabolomics
Peripheral plasma
Metabolic pathways
title Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis
title_full Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis
title_fullStr Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis
title_full_unstemmed Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis
title_short Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis
title_sort metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis staging and prognosis
topic Multiple myeloma
Biomarkers
Metabolomics
Peripheral plasma
Metabolic pathways
url https://doi.org/10.1186/s12967-024-05848-7
work_keys_str_mv AT xiaoxuewang metabolomicsapproachrevealskeyplasmabiomarkersinmultiplemyelomafordiagnosisstagingandprognosis
AT longhaocheng metabolomicsapproachrevealskeyplasmabiomarkersinmultiplemyelomafordiagnosisstagingandprognosis
AT aijunliu metabolomicsapproachrevealskeyplasmabiomarkersinmultiplemyelomafordiagnosisstagingandprognosis
AT lihongliu metabolomicsapproachrevealskeyplasmabiomarkersinmultiplemyelomafordiagnosisstagingandprognosis
AT liligong metabolomicsapproachrevealskeyplasmabiomarkersinmultiplemyelomafordiagnosisstagingandprognosis
AT guolinshen metabolomicsapproachrevealskeyplasmabiomarkersinmultiplemyelomafordiagnosisstagingandprognosis