Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as Potential Predictive Biomarkers for Chronic Graft vs. Host Disease

Author(s):Show less -

Alborghetti, Marcos Rodrigo ^[1] ; Pizzigatti Correa, Maria Elvira ^[2] ; Whangbo, Jennifer ^[3] ; Shi, Xu ^[4] ; Aricetti, Juliana Aparecida ^[5] ; da Silva, Andreia Aparecida ^[2] ; Martins Miranda, Eliana Cristina ^[2] ; Sforca, Mauricio Luis ^[6] ; Caldana, Camila ^[5] ; Gerszten, Robert E. ^[4] ; Ritz, Jerome ^[3] ; de Mattos Zeri, Ana Carolina ^[6]

Affiliation

^[1] Univ Brasilia, Dept Cell Biol, Brasilia, DF - Brazil

^[2] Univ Estadual Campinas, Inst Nacl Ciencia & Tecnol Sangue, Hematol & Hemotherapy Ctr, Hemoctr, Unicamp, Campinas, SP - Brazil

^[3] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 - USA

^[4] Harvard Med Sch, Beth Israel Deaconess Hosp, Boston, MA 02115 - USA

^[5] Brazillan Ctr Res Energy & Mat CNPEM, Brazilian Bioethanol Sci & Technol Lab CTBE, Campinas, SP - Brazil

^[6] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Campinas, SP - Brazil

• Document type: Journal article
• Source: FRONTIERS IN ONCOLOGY; v. 9, MAR 18 2019.
• Web of Science Citations: 1

Abstract

The allogeneic hematopoietic stem cell transplantation procedure-the only curative therapy for many types of hematological cancers-is increasing, and graft vs. host disease (GVHD) is the main cause of morbidity and mortality after transplantation. Currently, GVHD diagnosis is clinically performed. Whereas, biomarker panels have been developed for acute GVHD (aGVHD), there is a lack of information about the chronic form (cGVHD). Using nuclear magnetic resonance (NMR) and gas chromatography coupled to time-of-flight (GC-TOF) mass spectrometry, this study prospectively evaluated the serum metabolome of 18 Brazilian patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT). We identified and quantified 63 metabolites and performed the metabolomic profile on day -10, day 0, day +10 and day +100, in reference to day of transplantation. Patients did not present aGVHD or cGVHD clinical symptoms at sampling times. From 18 patients analyzed, 6 developed cGVHD. The branched-chain amino acids (BCAAs) leucine and isoleucine were reduced and the sulfur-containing metabolite (cystine) was increased at day +10 and day +100. The area under receiver operating characteristics (ROC) curves was higher than 0.79. BCAA findings were validated by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in 49 North American patients at day +100; however, cystine findings were not statistically significant in this patient set. Our results highlight the importance of multi-temporal and multivariate biomarker panels for predicting and understanding cGVHD. (AU)

• FAPESP's process: 11/06441-3 - Prospective analysis of the blood serum metabolome of patients undergoing bone marrow transplantation in the study of the GVHD (Graft-Versus-Host Disease)
• Grantee: Marcos Rodrigo Alborghetti
• Support Opportunities: Scholarships in Brazil - Post-Doctoral