Prediction of neuroblastoma cell response to treatment with natural or synthetic retinoids using selected protein biomarkers.

Viera Dobrotkova, Petr Chlapek, Marta Jezova, Katerina Adamkova, Pavel Mazanek, Jaroslav Sterba, Renata Veselska

Journal: PloS one 2020;14(6):e0218269

PMID: 31188873

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Abstract

Although the administration of retinoids represents an important part of treatment for children suffering from high-risk neuroblastomas, approximately 50% of these patients do not respond to this therapy or develop resistance to retinoids during treatment. Our study focused on the comparative analysis of the expression of five genes and corresponding proteins (DDX39A, HMGA1, HMGA2, HOXC9 and PBX1) that have recently been discussed as possible predictive biomarkers of clinical response to retinoid differentiation therapy. Expression of these five candidate biomarkers was evaluated at both the mRNA and protein level in the same subset of 8 neuroblastoma cell lines after treatment with natural or synthetic retinoids. We found that the cell lines that were HMGA2-positive and/or HOXC9-negative have a reduced sensitivity to retinoids. Furthermore, the experiments revealed that the retinoid-sensitive cell lines showed a uniform pattern of change after treatment with both natural and sensitive retinoids: increased DDX39A and decreased PBX1 protein levels. Our results showed that in NBL cells, these putative protein biomarkers are associated with sensitivity or resistance to retinoids, and their endogenous or induced expression can distinguish between these two phenotypes.

Address: Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital, Pekarska, Czech Republic.; Department of Pathology, University Hospital Brno and Faculty of Medicine, Masaryk University, Jihlavska, Czech Republic.; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Cernopolni, Czech Republic.

DOI: 10.1371/journal.pone.0218269

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MeSH Terms: Adolescent, Antineoplastic Agents, Bexarotene, Biomarkers, Pharmacological, Cell Line, Tumor, Cell Proliferation, Child, Child, Preschool, DEAD-box RNA Helicases, Drug Resistance, Neoplasm, Female, Fenretinide, HMGA1a Protein, HMGA2 Protein, Homeodomain Proteins, Humans, Infant, Infant, Newborn, Isotretinoin, Male, Nervous System Neoplasms, Neuroblastoma, Paraffin Embedding, Pre-B-Cell Leukemia Transcription Factor 1, Tissue Fixation, Tretinoin, Young Adult