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 language | English |
|---|---|
| Article number | 136 |
| Journal | Metabolomics |
| Volume | 13 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 1 Nov 2017 |
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Keywords
- B cell non-Hodgkin lymphoma
- Cerebrospinal fluid
- Leptomeningeal infiltration
- NMR metabolomics
- Serum
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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 journal › Article
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
UR - http://www.scopus.com/inward/record.url?scp=85030842168&partnerID=8YFLogxK
U2 - 10.1007/s11306-017-1269-9
DO - 10.1007/s11306-017-1269-9
M3 - Article
VL - 13
JO - Metabolomics
JF - Metabolomics
SN - 1573-3882
IS - 11
M1 - 136
ER -