title: Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study.
abstract: The prognosis for diffuse large B-cell lymphoma (DLBCL) patients with early relapse or refractory disease is dismal. To determine if clinical outcome correlated to diverse serum metabolomic profiles, we used (1)H nuclear magnetic resonance (NMR) spectroscopy and compared two groups of DLBCL patients treated with immunochemotherapy: i) refractory/early relapse (REF/REL; n=27) and ii) long-term progression-free (CURED; n = 60). A supervised multivariate analysis showed a separation between the groups. Among discriminating metabolites higher in the REF/REL group were the amino acids lysine and arginine, the degradation product cadaverine and a compound in oxidative stress (2-hydroxybutyrate). In contrast, the amino acids aspartate, valine and ornithine, and a metabolite in the glutathione cycle, pyroglutamate, were higher in CURED patients. Together, our data indicate that NMR-based serum metabolomics can identify a signature for DLBCL patients with high-risk of failing immunochemotherapy, prompting for larger validating studies which could lead to more individualized treatment of this disease.
authors.affiliation: a Section of Hematology, Department of Medicine , Kungälvs Hospital, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden ;
authors.forename: Martin
authors.initials: M
authors.lastname: Stenson
authors.affiliation: b Swedish NMR Centre, University of Gothenburg , Gothenburg , Sweden ;
authors.forename: Anders
authors.initials: A
authors.lastname: Pedersen
authors.affiliation: c Department of Research , Development and Education, Region Halland , Gothenburg , Sweden ;
authors.forename: Sverker
authors.initials: S
authors.lastname: Hasselblom
authors.affiliation: d Section of Hematology and Coagulation, Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg , Gothenburg , Sweden ;
authors.forename: Herman
authors.initials: H
authors.lastname: Nilsson-Ehle
authors.affiliation: b Swedish NMR Centre, University of Gothenburg , Gothenburg , Sweden ;
authors.forename: Bengt Göran
authors.initials: BG
authors.lastname: Karlsson
authors.affiliation: e Computational Life Science Cluster, Department of Clinical Chemistry , Umeå University, Umeå and Bioinformatics for Life Sciences (BILS) , Gothenburg , Sweden ;
authors.forename: Rui
authors.initials: R
authors.lastname: Pinto
authors.affiliation: f Unit of Hematology, Department of Medicine , Södra Älvsborg Hospital Borås, Sahlgrenska Academy at the University of Gothenburg , Gothenburg , Sweden.
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Andersson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000097:blood; D001224:Aspartic Acid / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002103:Cadaverine / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D008239:Lysine / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000401:mortality; D009952:Ornithine / Q000097:blood; D010865:Pilot Projects; D011379:Prognosis; D011761:Pyrrolidonecarboxylic Acid / Q000097:blood; D016896:Treatment Outcome; D014633:Valine / Q000097:blood; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D006885:Hydroxybutyrates; D007166:Immunosuppressive Agents; D001224:Aspartic Acid; D001120:Arginine; D009952:Ornithine; D014633:Valine; D008239:Lysine; D002103:Cadaverine; D011761:Pyrrolidonecarboxylic Acid
keywords: DLBCL; metabolomics; outcome; serum