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Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
Metabolic Pathways Associated With Psychoneurological Symptoms in Children With Cancer Receiving Chemotherapy
Jinbing Bai1,2, Janice Withycombe3, Ronald C Eldridge1
1Nell Hodgson Woodruff School of Nursing, 1371Emory University, Atlanta, GA, USA.
Insights
Chemotherapy in children with cancer can cause psychoneurological symptoms (PNS). Metabolomics revealed associations between fatty acid and amino acid pathways and PNS, offering new insights into symptom management.
Area of Science:
- Biochemistry
- Oncology
- Pediatrics
Background:
- Children with cancer undergoing chemotherapy often experience a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, and depressive symptoms.
- Metabolomics offers a promising approach to identify metabolic pathways linked to these symptoms.
Purpose of the Study:
- To identify specific metabolic pathways associated with the psychoneurological symptom cluster in pediatric cancer patients before and after chemotherapy.
- To explore the relationship between serum metabolites and symptoms of pain, fatigue, anxiety, and depression.
Main Methods:
- Utilized the Pediatric PROMIS scales to assess pain, fatigue, anxiety, and depressive symptoms.
- Employed an untargeted metabolomics approach using liquid chromatography-mass spectrometry on serum samples.
- Applied linear regression models and metabolic pathway enrichment analysis to identify associations.
Main Results:
- Identified 9276 unique metabolic features associated with individual symptoms and the overall PNS cluster.
- Fatty acid pathways (e.g., de novo fatty acid biosynthesis, omega-3 fatty acid metabolism) were significantly associated with pain.
- The tryptophan amino acid pathway was linked to fatigue, anxiety, and the overall PNS cluster, while the carnitine shuttle was associated with the PNS cluster.
Conclusions:
- Fatty acid and amino acid metabolic pathways are significantly associated with psychoneurological symptoms in children undergoing chemotherapy.
- These findings highlight potential biomarkers and therapeutic targets for managing PNS in pediatric cancer patients.
- Further validation in larger cohorts is warranted to confirm these associations.
Context:
Children with cancer undergoing chemotherapy experience a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, and depressive symptoms. Metabolomics is promising to differentiate metabolic pathways associated with the PNS cluster.
Objectives:
Identify metabolic pathways associated with the PNS cluster in children with cancer before and after chemotherapy.
Methods:
Pain, fatigue, anxiety, and depressive symptoms were assessed using the Pediatric PROMIS scales. T-scores were computed and divided dichotomously by a cutoff point of 50; the PNS cluster was a sum of the four symptoms ranging from 0 (all T-scores <50) to 4 (all T-scores ≥50). Serum metabolites were processed using liquid chromatography mass-spectrometry untargeted metabolomics approach. Linear regression models examined metabolites associated with the PNS cluster. Metabolic pathway enrichment analysis was performed.
Results:
Participant demographics (n = 40) were 55% female, 60% white, 62.5% aged 13-19 years, and 62.5% diagnoses of Hodgkin's lymphoma and B-cell acute lymphocytic leukemia. Among 9276 unique metabolic features, 454 were associated with pain, 281 with fatigue, 596 with anxiety, 551 with depressive symptoms, and 300 with the PNS cluster across one chemotherapy cycle. Fatty acids pathways were associated with pain: de novo fatty acid biosynthesis (p < .001), fatty acid metabolism (p = .001), fatty acid activation (p = .004), and omega-3 fatty acid metabolism (p = .009). Tryptophan amino acid pathway was associated with fatigue (p < .001), anxiety (p = .015), and the PNS cluster (p = .037). Carnitine shuttle was associated with the PNS cluster (p = .015).
Conclusion:
Fatty acids and amino acids pathways were associated with PNS in children undergoing chemotherapy. These findings require further investigation in a larger sample.
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