Integration of metabolomics and transcriptomics reveals convergent pathways driving radiation-induced salivary gland dysfunction
AffiliationDepartment of Nutritional Sciences, University of Arizona
Bioinformatics Shared Resource, Arizona Cancer Center, University of Arizona
University of Arizona Cancer Center
Department of Molecular and Cellular Biology, University of Arizona
MetadataShow full item record
PublisherAmerican Physiological Society
CitationMeeks, L., De Oliveira Pessoa, D., Martinez, J. A., Limesand, K. H., & Padi, M. (2021). Integration of metabolomics and transcriptomics reveals convergent pathways driving radiation-induced salivary gland dysfunction. Physiological Genomics, 53(3), 85-98.
Rights©2021 the American Physiological Society
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AbstractRadiation therapy for head and neck cancer causes damage to the surrounding salivary glands, resulting in salivary gland hypofunction and xerostomia. Current treatments do not provide lasting restoration of salivary gland function following radiation; therefore, a new mechanistic understanding of the radiation-induced damage response is necessary for identifying therapeutic targets. The purpose of the present study was to investigate the metabolic phenotype of radiation-induced damage in parotid salivary glands by integrating transcriptomic and metabolomic data. Integrated data were then analyzed to identify significant gene-metabolite interactions. Mice received a single 5 Gy dose of targeted head and neck radiation. Parotid tissue samples were collected 5 days following treatment for RNA sequencing and metabolomics analysis. Altered metabolites and transcripts significantly converged on a specific region in the metabolic reaction network. Both integrative pathway enrichment using rank-based statistics and network analysis highlighted significantly coordinated changes in glutathione metabolism, energy metabolism (TCA cycle and thermogenesis), peroxisomal lipid metabolism, and bile acid production with radiation. Integrated changes observed in energy metabolism suggest that radiation induces a mitochondrial dysfunction phenotype. These findings validated previous pathways involved in the radiation-damage response, such as altered energy metabolism, and identified robust signatures in salivary glands, such as reduced glutathione metabolism, that may be driving salivary gland dysfunction.
Note12 month embargo; first published online 15 March 2021
VersionFinal accepted manuscript
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