J Clin Neurol.  2019 Oct;15(4):511-516. 10.3988/jcn.2019.15.4.511.

Prediction of Chemotherapy-Induced Peripheral Neuropathy in Patients with Lymphoma and Myeloma: the Roles of Brain-Derived Neurotropic Factor Protein Levels and A Gene Polymorphism

• Azoulay D
• Giryes S
• Nasser R
• Sharon R
• Horowitz N

• KMID: 2467761
• DOI: http://doi.org/10.3988/jcn.2019.15.4.511

Abstract

BACKGROUND AND PURPOSE
Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that plays an essential role in the maintenance of the nervous system. We have evaluated the peripheral blood protein levels of BDNF and the valine-to-methionine substitution at codon 66 (Val66Met) single-nucleotide polymorphism (SNP) as potential biomarkers for the early recognition of chemotherapy-induced peripheral neuropathy (CIPN) in non-Hodgkin lymphoma and multiple myeloma patients.
METHODS
CIPN was assessed in 45 patients at the diagnosis and during vincristine or bortezomib-based therapy using objective [reduced version of the Total Neuropathy Score (TNSr)] and subjective (FACT-GOG-NTx) tools. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) questionnaire. BDNF protein levels and the Val66Met SNP were determined using ELISA and Sanger sequencing.
RESULTS
The pretreatment BDNF protein level was inversely correlated with the maximum TNSr, FACT-GOG-NTx, and PHQ-9 scores in both genotypes. BDNF patients with the Val/Val genotype demonstrated significantly higher maximum FACT-GOG-NTx and PHQ-9 scores than those with the Val/Met and Met/Met genotypes (Met-BNDF carriers). Correlations between PHQ-9 and TNSr score were found only in Met-BDNF carriers, suggesting that peripheral neuropathy and depression coincide in Met-BDNF carriers.
CONCLUSIONS
Determining the BDNF protein levels before initiating chemotherapy might be a useful tool for CIPN risk assessment and preemptive dose modification. The present data should be validated in larger studies that include other neurotoxic agents.

Keyword

BDNF; chemotherapy-induced peripheral neuropathy; Val66Met single-nucleotide polymorphism; non-Hodgkin lymphoma; multiple myeloma

MeSH Terms

Biomarkers
Brain-Derived Neurotrophic Factor
Codon
Depression
Diagnosis
Drug Therapy
Enzyme-Linked Immunosorbent Assay
Genes, vif*
Genotype
Humans
Lymphoma*
Lymphoma, Non-Hodgkin
Multiple Myeloma
Nervous System
Neurons
Peripheral Nervous System Diseases*
Risk Assessment
Vincristine
Biomarkers
Brain-Derived Neurotrophic Factor
Codon
Vincristine

Figure

• 

  Fig. 1 Correlations between the pretreatment BDNF level and the objective symptoms (A), subjective symptoms (B), and depression (C) in CIPN patients. The graphs include linear regression lines for the relationships between pretreatment BDNF levels and the maximum TNSr, FACT-GOG-NTx, and PHQ-9 scores. BDNF: brain-derived neurotrophic factor, CIPN: chemotherapy-induced peripheral neuropathy, FACT-GOG-NTx: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, PHQ-9: Patient Health Questionnaire-9, TNSr: reduced version of the Total Neuropathy Score.

• 

  Fig. 2 Baseline and maximum FACT-GOG-NTx scores (A) and PHQ-9 scores in Val-BDNF and Met-BDNF patients (B). Data are mean and SEM values. *p<0.05, †p<0.01. BDNF: brain-derived neurotrophic factor, FACT-GOG-NTx: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, PHQ-9: Patient Health Questionnaire-9.

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