An assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcoma
Background: 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 sa...
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Elsevier
2025-06-01
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| Series: | EJC Paediatric Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772610X25000030 |
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| author | Pawan Gulati Vickyanne Carruthers Claire Hutton Chloe Cassidy Edward B. Amankwatia Séréna Pascual Electra Florence Tsegay G. Gebru Andrea L. Jorgensen Alastair Greystoke Guy Makin Martin G. McCabe Daniel B. Hawcutt Gareth J. Veal David Jamieson |
| author_facet | Pawan Gulati Vickyanne Carruthers Claire Hutton Chloe Cassidy Edward B. Amankwatia Séréna Pascual Electra Florence Tsegay G. Gebru Andrea L. Jorgensen Alastair Greystoke Guy Makin Martin G. McCabe Daniel B. Hawcutt Gareth J. Veal David Jamieson |
| author_sort | Pawan Gulati |
| collection | DOAJ |
| description | Background: 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. |
| format | Article |
| id | doaj-art-cde8e58f28734f028ac7234e38425c3d |
| institution | Kabale University |
| issn | 2772-610X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EJC Paediatric Oncology |
| spelling | doaj-art-cde8e58f28734f028ac7234e38425c3d2025-01-25T04:11:29ZengElsevierEJC Paediatric Oncology2772-610X2025-06-015100216An assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcomaPawan Gulati0Vickyanne Carruthers1Claire Hutton2Chloe Cassidy3Edward B. Amankwatia4Séréna Pascual5Electra Florence6Tsegay G. Gebru7Andrea L. Jorgensen8Alastair Greystoke9Guy Makin10Martin G. McCabe11Daniel B. Hawcutt12Gareth J. Veal13David Jamieson14Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UKNewcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK; Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UKNewcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UKNewcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UKNewcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UKNewcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UKNewcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UKDepartment of Health Data Science, Institute of Population Health, University of Liverpool, UKDepartment of Health Data Science, Institute of Population Health, University of Liverpool, UKNewcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK; Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UKDivision of Cancer Sciences, University of Manchester, Manchester, UK; Royal Manchester Children's Hospital, Manchester, UKDivision of Cancer Sciences, University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UKDepartment of Women’s and Children’s Health, University of Liverpool, UK; Alder Hey Children’s Hospital, Liverpool, UKNewcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UKNewcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK; Correspondence to: Newcastle University Centre for Cancer Research, Paul O′Gorman Building, Newcastle University, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.Background: 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.http://www.sciencedirect.com/science/article/pii/S2772610X25000030Ewing sarcomaMucositisChemotherapy |
| spellingShingle | Pawan Gulati Vickyanne Carruthers Claire Hutton Chloe Cassidy Edward B. Amankwatia Séréna Pascual Electra Florence Tsegay G. Gebru Andrea L. Jorgensen Alastair Greystoke Guy Makin Martin G. McCabe Daniel B. Hawcutt Gareth J. Veal David Jamieson An assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcoma EJC Paediatric Oncology Ewing sarcoma Mucositis Chemotherapy |
| title | An assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcoma |
| title_full | An assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcoma |
| title_fullStr | An assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcoma |
| title_full_unstemmed | An assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcoma |
| title_short | An assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcoma |
| title_sort | assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in ewing sarcoma |
| topic | Ewing sarcoma Mucositis Chemotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2772610X25000030 |
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