Identification of putative biomarkers for leptomeningeal invasion in B-cell non-Hodgkin lymphoma by NMR metabolomics

Gonçalo Graça, Joana Desterro, Joana Sousa, Carlos Fonseca, Margarida Silveira, Jacinta Serpa, Tânia Carvalho, Maria G. da Silva, L.G. Goncalves

Research output: Contribution to journalArticle

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Abstract

Introduction: B-cell non-Hodgkin lymphoma (B-NHL) is the most common hematological malignancy and different genetic alterations are frequently detected in transformed B lymphocytes. Within this heterogeneous disease, certain aggressive subgroups have an increased risk of central nervous system (CNS) involvement at diagnosis and/or relapse, resulting in parenchymal or leptomeningeal infiltration (LI) in 5–15% of cases. The current sensitivity limitations of cerebrospinal fluid (CSF) cytology and contrast-enhanced MRI for CNS involvement, mainly at early stages, motivates the search for alternative diagnostic methods. Objectives: Here we aim at using untargeted 1H-NMR metabolomics to identify putative biomarkers for LI in B-NHL patients. Methods: CSF and peripheral blood samples were obtained from B-NHL patients with a positive (n = 7, LI group) or negative LI diagnostic (n = 13, control group). For seven patients, CSF samples were collected during the course of intrathecal chemotherapy, making it possible to assess the patient´s response to treatment. 1H-NMR spectra were acquired and statistical multivariate and univariate analysis were performed to identify significant alterations. Results: Significant metabolite differences were found between LI and control groups in CSF, but not in serum. A predictive PLS-DA cross-validated model identified significant pool changes in glycine, alanine, pyruvate, acetylcarnitine, carnitine, and phenylalanine. Additionally, increments in protein signals were detected in the LI group. Significantly, the PLS-DA model predicted correctly all samples obtained from the group of patients in remission during LI treatment. Conclusions: The results show that the CSF NMR-metabolomics approach is a promising complementary method in clinical diagnosis and treatment follow-up of LI in B-NHL patients.

Original languageEnglish
Article number136
JournalMetabolomics
Volume13
Issue number11
DOIs
Publication statusPublished - 1 Nov 2017

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Metabolomics
B-Cell Lymphoma
Biomarkers
Infiltration
Non-Hodgkin's Lymphoma
Cerebrospinal fluid
Cells
Cerebrospinal Fluid
Nuclear magnetic resonance
Neurology
Central Nervous System
Acetylcarnitine
Control Groups
Carnitine
Cytology
Hematologic Neoplasms
Pyruvic Acid
Phenylalanine
Alanine
Glycine

Keywords

  • B cell non-Hodgkin lymphoma
  • Cerebrospinal fluid
  • Leptomeningeal infiltration
  • NMR metabolomics
  • Serum

Cite this

Graça, Gonçalo ; Desterro, Joana ; Sousa, Joana ; Fonseca, Carlos ; Silveira, Margarida ; Serpa, Jacinta ; Carvalho, Tânia ; da Silva, Maria G. ; Goncalves, L.G. / Identification of putative biomarkers for leptomeningeal invasion in B-cell non-Hodgkin lymphoma by NMR metabolomics. In: Metabolomics. 2017 ; Vol. 13, No. 11.
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abstract = "Introduction: B-cell non-Hodgkin lymphoma (B-NHL) is the most common hematological malignancy and different genetic alterations are frequently detected in transformed B lymphocytes. Within this heterogeneous disease, certain aggressive subgroups have an increased risk of central nervous system (CNS) involvement at diagnosis and/or relapse, resulting in parenchymal or leptomeningeal infiltration (LI) in 5–15{\%} of cases. The current sensitivity limitations of cerebrospinal fluid (CSF) cytology and contrast-enhanced MRI for CNS involvement, mainly at early stages, motivates the search for alternative diagnostic methods. Objectives: Here we aim at using untargeted 1H-NMR metabolomics to identify putative biomarkers for LI in B-NHL patients. Methods: CSF and peripheral blood samples were obtained from B-NHL patients with a positive (n = 7, LI group) or negative LI diagnostic (n = 13, control group). For seven patients, CSF samples were collected during the course of intrathecal chemotherapy, making it possible to assess the patient´s response to treatment. 1H-NMR spectra were acquired and statistical multivariate and univariate analysis were performed to identify significant alterations. Results: Significant metabolite differences were found between LI and control groups in CSF, but not in serum. A predictive PLS-DA cross-validated model identified significant pool changes in glycine, alanine, pyruvate, acetylcarnitine, carnitine, and phenylalanine. Additionally, increments in protein signals were detected in the LI group. Significantly, the PLS-DA model predicted correctly all samples obtained from the group of patients in remission during LI treatment. Conclusions: The results show that the CSF NMR-metabolomics approach is a promising complementary method in clinical diagnosis and treatment follow-up of LI in B-NHL patients.",
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Identification of putative biomarkers for leptomeningeal invasion in B-cell non-Hodgkin lymphoma by NMR metabolomics. / Graça, Gonçalo; Desterro, Joana; Sousa, Joana; Fonseca, Carlos; Silveira, Margarida; Serpa, Jacinta; Carvalho, Tânia; da Silva, Maria G.; Goncalves, L.G.

In: Metabolomics, Vol. 13, No. 11, 136, 01.11.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of putative biomarkers for leptomeningeal invasion in B-cell non-Hodgkin lymphoma by NMR metabolomics

AU - Graça, Gonçalo

AU - Desterro, Joana

AU - Sousa, Joana

AU - Fonseca, Carlos

AU - Silveira, Margarida

AU - Serpa, Jacinta

AU - Carvalho, Tânia

AU - da Silva, Maria G.

AU - Goncalves, L.G.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Introduction: B-cell non-Hodgkin lymphoma (B-NHL) is the most common hematological malignancy and different genetic alterations are frequently detected in transformed B lymphocytes. Within this heterogeneous disease, certain aggressive subgroups have an increased risk of central nervous system (CNS) involvement at diagnosis and/or relapse, resulting in parenchymal or leptomeningeal infiltration (LI) in 5–15% of cases. The current sensitivity limitations of cerebrospinal fluid (CSF) cytology and contrast-enhanced MRI for CNS involvement, mainly at early stages, motivates the search for alternative diagnostic methods. Objectives: Here we aim at using untargeted 1H-NMR metabolomics to identify putative biomarkers for LI in B-NHL patients. Methods: CSF and peripheral blood samples were obtained from B-NHL patients with a positive (n = 7, LI group) or negative LI diagnostic (n = 13, control group). For seven patients, CSF samples were collected during the course of intrathecal chemotherapy, making it possible to assess the patient´s response to treatment. 1H-NMR spectra were acquired and statistical multivariate and univariate analysis were performed to identify significant alterations. Results: Significant metabolite differences were found between LI and control groups in CSF, but not in serum. A predictive PLS-DA cross-validated model identified significant pool changes in glycine, alanine, pyruvate, acetylcarnitine, carnitine, and phenylalanine. Additionally, increments in protein signals were detected in the LI group. Significantly, the PLS-DA model predicted correctly all samples obtained from the group of patients in remission during LI treatment. Conclusions: The results show that the CSF NMR-metabolomics approach is a promising complementary method in clinical diagnosis and treatment follow-up of LI in B-NHL patients.

AB - Introduction: B-cell non-Hodgkin lymphoma (B-NHL) is the most common hematological malignancy and different genetic alterations are frequently detected in transformed B lymphocytes. Within this heterogeneous disease, certain aggressive subgroups have an increased risk of central nervous system (CNS) involvement at diagnosis and/or relapse, resulting in parenchymal or leptomeningeal infiltration (LI) in 5–15% of cases. The current sensitivity limitations of cerebrospinal fluid (CSF) cytology and contrast-enhanced MRI for CNS involvement, mainly at early stages, motivates the search for alternative diagnostic methods. Objectives: Here we aim at using untargeted 1H-NMR metabolomics to identify putative biomarkers for LI in B-NHL patients. Methods: CSF and peripheral blood samples were obtained from B-NHL patients with a positive (n = 7, LI group) or negative LI diagnostic (n = 13, control group). For seven patients, CSF samples were collected during the course of intrathecal chemotherapy, making it possible to assess the patient´s response to treatment. 1H-NMR spectra were acquired and statistical multivariate and univariate analysis were performed to identify significant alterations. Results: Significant metabolite differences were found between LI and control groups in CSF, but not in serum. A predictive PLS-DA cross-validated model identified significant pool changes in glycine, alanine, pyruvate, acetylcarnitine, carnitine, and phenylalanine. Additionally, increments in protein signals were detected in the LI group. Significantly, the PLS-DA model predicted correctly all samples obtained from the group of patients in remission during LI treatment. Conclusions: The results show that the CSF NMR-metabolomics approach is a promising complementary method in clinical diagnosis and treatment follow-up of LI in B-NHL patients.

KW - B cell non-Hodgkin lymphoma

KW - Cerebrospinal fluid

KW - Leptomeningeal infiltration

KW - NMR metabolomics

KW - Serum

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