Metabolomics Approach Reveals Key Plasma Biomarkers for Tumor Biology in Multiple Myeloma

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 thirty-three HC, thirty-eight newly diagnosed MM patients (NDMM) categorized into three RISS grades (grade I: n = 5; grade II: n = 19; grade III: n = 8), and ninety-two MM patients post-targeted therapy with bortezomib-based regimens. 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, seventy metabolites, primarily associated with the citrate cycle, amino acids and glycerophospholipid/sphingolipid metabolism, and nine metabolic pathways (citrate cycle, choline metabolism, glyceropholipid metabolism, sphingolipid metabolism, valine, leucine and isoleucine biosynthesis, etc.) exhibited significant changes in NDMM. Notably, lactic acid and leucine have emerged not only as diagnostic biomarkers but also as markers for tumor monitoring in staging and prognosis, respectively. 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.