Nontargeted and targeted metabolomics approaches reveal the key amino acid alterations involved in multiple myeloma

Lingling Yue; Pengyun Zeng; Yanhong Li; Ye Chai; Chongyang Wu; Bingren Gao

doi:10.7717/peerj.12918

Nontargeted and targeted metabolomics approaches reveal the key amino acid alterations involved in multiple myeloma

PeerJ. 2022 Feb 9:10:e12918. doi: 10.7717/peerj.12918. eCollection 2022.

Authors

Lingling Yue¹, Pengyun Zeng¹, Yanhong Li², Ye Chai¹, Chongyang Wu¹, Bingren Gao³

Affiliations

¹ Department of Hematology, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
² Institute of Hematology, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
³ Department of Cardiac Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

Abstract

Purpose: Multiple myeloma (MM), a kind of malignant neoplasm of clonal plasma cells in the bone marrow, is a refractory disease. Understanding the metabolism disorders and identification of metabolomics pathways as well as key metabolites will provide new insights for exploring diagnosis and therapeutic targets of MM.

Methods: We conducted nontargeted metabolomics analysis of MM patients and normal controls (NC) using ultra-high-performance liquid chromatography (UHPLC) combined with quadrupole time-of-flight mass spectrometry (Q-TOF-MS) in 40 cases of cohort 1 subjects. The targeted metabolomics analysis of amino acids using multiple reaction monitoring-mass spectrometry (MRM-MS) was also performed in 30 cases of cohort 1 and 30 cases of cohort 2 participants, to comprehensively investigate the metabolomics disorders of MM.

Results: The nontargeted metabolomics analysis in cohort 1 indicated that there was a significant metabolic signature change between MM patients and NC. The differential metabolites were mainly enriched in metabolic pathways related to amino acid metabolism, such as protein digestion and absorption, and biosynthesis of amino acids. Further, the targeted metabolomics analysis of amino acids in both cohort 1 and cohort 2 revealed differential metabolic profiling between MM patients and NC. We identified 12 and 14 amino acid metabolites with altered abundance in MM patients compared to NC subjects, in cohort 1 and cohort 2, respectively. Besides, key differential amino acid metabolites, such as choline, creatinine, leucine, tryptophan, and valine, may discriminate MM patients from NC. Moreover, the differential amino acid metabolites were associated with clinical indicators of MM patients.

Conclusions: Our findings indicate that amino acid metabolism disorders are involved in MM. The differential profiles reveal the potential utility of key amino acid metabolites as diagnostic biomarkers of MM. The alterations in metabolome, especially the amino acid metabolome, may provide more evidences for elucidating the pathogenesis and development of MM.

Keywords: Diagnostic biomarkers; Differential amino acid metabolites; Metabolic pathways; Metabolomics profiles; Multiple myeloma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids* / metabolism
Humans
Mass Spectrometry
Metabolome
Metabolomics / methods
Multiple Myeloma* / diagnosis

Substances

Amino Acids

Associated data

figshare/10.6084/m9.figshare.14904135

Grants and funding

This work was supported by the Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital, CY2017-MS13. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.