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Lookup NU author(s): Dr Pawan Gulati, Dr Vickyanne Carruthers, Dr Claire Hutton, Chloe Cassidy, Dr Edward Amankwatia, Séréna Pascual, Electra Florence, Professor Alastair GreystokeORCiD, Professor Gareth Veal, Dr David Jamieson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The AuthorsBackground: Treatment of Ewing sarcoma is associated with severe toxicities including chemotherapy-induced mucositis. Here we investigated the role of circulating biomarkers and genetic factors in predicting mucositis severity in Ewing sarcoma. Methods: Blood samples were collected from 111 Ewing sarcoma patients during treatment. Circulating total CK18 and FLT3 ligand concentrations were measured in plasma. Germline DNA was used to investigate associations between genetic variants and mucositis severity. Results: An increase in median tCK18 levels was observed during cycle 1, from 189 (86−736) U/L at cycle 1 day 1 pre-chemotherapy to 311 (141–1138) U/L on cycle 1 day 2–5 (p = 0.0001). Patients experiencing a ≥ 1.3-fold increase in tCK18 at 48–120 hours after administration of the first cycle had a higher likelihood of developing grade 3 mucositis in any cycle (p = 0.044). Genetic analysis revealed an association between a gene set associated with chemotherapy induced severe mucositis and differentially expressed genes set for minor salivary gland (p = 4.12 ×10−4) and esophageal mucosa (p = 1.55 ×10−5). Discussion: Early increases in circulating CK18 levels correlated with grade 3 mucositis. Genome-wide association analysis highlighted genes that may be associated with mucositis pathology, offering insights into biological mechanisms underlying susceptibility.
Author(s): Gulati P, Carruthers V, Hutton C, Cassidy C, Amankwatia EB, Pascual S, Florence E, Gebru TG, Jorgensen AL, Greystoke A, Makin G, McCabe MG, Hawcutt DB, Veal GJ, Jamieson D
Publication type: Article
Publication status: Published
Journal: EJC Paediatric Oncology
Year: 2025
Volume: 5
Print publication date: 01/06/2025
Online publication date: 20/01/2025
Acceptance date: 14/01/2025
Date deposited: 03/02/2025
ISSN (electronic): 2772-610X
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.ejcped.2025.100216
DOI: 10.1016/j.ejcped.2025.100216
Data Access Statement: Supplementary data associated with this article can be found in the online version at doi:10.1016/j.ejcped.2025.100216
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