Cited by 12Sarcoma Diagnosis and TreatmentAdvanced Proteomics Techniques and ApplicationsAcute Lymphoblastic Leukemia research

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Detection of early prognostic biomarkers for metastasis of Ewing's sarcoma in pediatric patients

Abstract

Aims Ewing's Sarcoma is an extremely aggressive tumor in children. The disease is associated with highly metastatic rate, especially at the time of diagnosis, contributing to a lower survival rate and poor prognosis. The study aimed to identify predictive biomarkers for metastatic Ewing's sarcoma through in-depth analysis of the plasma proteome profile of pediatric Ewing's sarcoma patients. Main methods Plasma samples from Ewing's sarcoma patients and control individuals were profiled using both shotgun and dimethyl-labeled proteomics analysis. Subsequently, Ewing's sarcoma patients were further stratified according to their metastatic state and chemotherapy response. Western blot was used for validation. Univariate and multivariate analyses were performed to determine proteome metastasis predictors. Receiver operating characteristic (ROC) analysis was done to assess the diagnostic significance of the potential plasma Ewing's sarcoma biomarkers. Key findings Our results revealed a set of proteins significantly associated with the metastatic Ewing's sarcoma disease profile. These proteins include ceruloplasmin and several immunoglobulins. Additionally, our study disclosed significant differentially expressed proteins in pediatric Ewing's sarcoma, including CD5 antigen-like, clusterin, and dermcidin. Stable isotope dimethyl labeling and western blot further confirmed our results, strengthening the impact of such proteins in disease development. Furthermore, an unbiased ROC curve evaluated and confirmed the predictive power of these biomarker candidates. Significance This study presented potential empirical predictive circulating biomarkers for determining the disease status of pediatric Ewing's sarcoma, which is vital for early prediction.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.lfs.2023.122237

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 1 references

Research works printed but not linked: 57

  1. Balamuth, 2010, Ewing’s sarcoma, Lancet Oncol., 11, 184, 10.1016/S1470-2045(09)70286-4 · DOI
  2. Samuel, 2020, Ewing sarcoma family of tumors-derived small extracellular vesicle proteomics identify potential clinical biomarkers, Oncotarget, 11, 2995, 10.18632/oncotarget.27678 · DOI
  3. Randall, 2010, Is there a predisposition gene for Ewing’s sarcoma?, J. Oncol., 2010, 10.1155/2010/397632 · DOI
  4. Tu, 2017, The Histogenesis of Ewing sarcoma, Cancer Rep Rev., 1, 10.15761/CRR.1000111 · DOI
  5. Kondo, 2019, Current status of proteomics in Ewing’s sarcoma, Proteomics Clin. Appl., 13
  6. Madoz-Gúrpide, 2016, Proteomic profiling of Ewing sarcoma reveals a role for TRAF6 in proliferation and ribonucleoproteins, RNA Processing J Proteomics Bioinform., 9, 166
  7. Riggi, 2007, The biology of Ewing sarcoma, Cancer Lett., 254, 1, 10.1016/j.canlet.2006.12.009 · DOI
  8. Ramos-Rivera, 2016, Extraskeletal Ewing sarcoma of the parapharyngeal space with a unique translocation, t(19;22) (q13.4;q12.2), Human Pathology: Case Reports., 4, 38
  9. Shulman, 2022, An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma, npj Precision Oncology., 6, 65, 10.1038/s41698-022-00307-2 · DOI
  10. Khanna, 2017, Metastatic Ewing’s sarcoma: revisiting the “evidence on the fence”, Indian Journal of Medical and Paediatric Oncology, 38, 173
  11. Kikuta, 2009, Nucleophosmin as a candidate prognostic biomarker of Ewing’s sarcoma revealed by proteomics, Clinical Cancer Research, 15, 2885, 10.1158/1078-0432.CCR-08-1913 · DOI
  12. Grunewald, 2012, STEAP1 is associated with the invasive and oxidative stress phenotype of Ewing tumors, Molecular cancer research : MCR., 10, 52, 10.1158/1541-7786.MCR-11-0524 · DOI
  13. Womer, 2012, Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children’s oncology group, J. Clin. Oncol., 30, 4148, 10.1200/JCO.2011.41.5703 · DOI
  14. Huynh, 2009, Tryptic digestion of in-gel proteins for mass spectrometry analysis, Methods in Molecular Biology (Clifton, NJ)., 519, 507, 10.1007/978-1-59745-281-6_34 · DOI
  15. Boersema, 2009, Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics, Nat. Protoc., 4, 484, 10.1038/nprot.2009.21 · DOI
  16. Dieterle, 2006, Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics, Anal. Chem., 78, 4281, 10.1021/ac051632c · DOI
  17. Benjamini, 1995, Controlling the false discovery rate: a practical and powerful approach to multiple testing, J. R. Stat. Soc. B. Methodol., 57, 289, 10.1111/j.2517-6161.1995.tb02031.x · DOI · Paper page
  18. Roumeliotis, 2017, Genomic determinants of protein abundance variation in colorectal Cancer cells, Cell Rep., 20, 2201, 10.1016/j.celrep.2017.08.010 · DOI
  19. Vera-Montecinos, 2021, Analysis of molecular networks in the cerebellum in chronic schizophrenia: modulation by early postnatal life stressors in murine models, Int. J. Mol. Sci., 22, 10076, 10.3390/ijms221810076 · DOI
  20. Lê Cao, 2011, Sparse PLS discriminant analysis: biologically relevant feature selection and graphical displays for multiclass problems, BMC Bioinformatics., 12, 253, 10.1186/1471-2105-12-253 · DOI
  21. Cawley, 2004, Fast exact leave-one-out cross-validation of sparse least-squares support vector machines, Neural Networks, 17, 1467, 10.1016/j.neunet.2004.07.002 · DOI
  22. Soudy, 2020, UniprotR: retrieving and visualizing protein sequence and functional information from universal protein resource (UniProt knowledgebase), J. Proteomics, 213, 10.1016/j.jprot.2019.103613 · DOI
  23. Raudvere, 2019, g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update), Nucleic Acids Res., 47, 10.1093/nar/gkz369 · DOI · Paper page
  24. Liberzon, 2011, Molecular signatures database (MSigDB) 3.0, Bioinformatics (Oxford, England), 27, 1739
  25. Szklarczyk, 2019, STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets, Nucleic Acids Res., 47, 10.1093/nar/gky1131 · DOI · Paper page
  26. Eikeland, 1971, On the generality of univariate eta, Scand. J. Educ. Res., 15, 149, 10.1080/0031383710150109 · DOI
  27. Xu, 2001, Monte Carlo cross validation, Chemom. Intel. Lab. Syst., 56, 1, 10.1016/S0169-7439(00)00122-2 · DOI
  28. Bernstein, 2006, Ewing’s sarcoma family of tumors: current management, Oncologist, 11, 503, 10.1634/theoncologist.11-5-503 · DOI
  29. Aran, 2018, CD5L is upregulated in hepatocellular carcinoma and promotes liver cancer cell proliferation and antiapoptotic responses by binding to HSPA5 (GRP78), FASEB J., 32, 3878, 10.1096/fj.201700941RR · DOI
  30. Li, 2011, Api6/AIM/Spα/CD5L overexpression in alveolar type II epithelial cells induces spontaneous lung adenocarcinoma, Cancer Res., 71, 5488, 10.1158/0008-5472.CAN-10-4225 · DOI
  31. Lee Motoyama, 2007, Identification of dermcidin in human gestational tissue and characterization of its proteolytic activity, Biochem. Biophys. Res. Commun., 357, 828, 10.1016/j.bbrc.2007.03.112 · DOI
  32. Bancovik, 2015, Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling, BMC Cancer, 15, 70, 10.1186/s12885-015-1022-6 · DOI
  33. Qiu, 2022, Dermcidin enhances the migration, invasion, and metastasis of hepatocellular carcinoma cells in vitro and in vivo, J. Clin. Transl. Hepatol., 10, 429, 10.14218/JCTH.2021.00108 · DOI
  34. Choi, 2016, Hornerin is involved in breast Cancer progression, J. Breast Cancer, 19, 142, 10.4048/jbc.2016.19.2.142 · DOI
  35. Rao, 2013, Distinct profiles of oxidative stress-related and matrix proteins in adult bone and soft tissue osteosarcoma and desmoid tumors: a proteomics study, Hum. Pathol., 44, 725, 10.1016/j.humpath.2012.06.023 · DOI
  36. Lourda, 2007, Development of resistance to chemotherapeutic drugs in human osteosarcoma cell lines largely depends on up-regulation of clusterin/apolipoprotein, J. International Journal of Cancer., 120, 611
  37. Kususda, 2012, Clusterin inhibition using OGX-011 synergistically enhances antitumour activity of sorafenib in a human renal cell carcinoma model, Br. J. Cancer, 106, 1945, 10.1038/bjc.2012.209 · DOI
  38. Cao, 2005, Clusterin as a therapeutic target for radiation sensitization in a lung cancer model, Int. J. Radiat. Oncol. Biol. Phys., 63, 1228, 10.1016/j.ijrobp.2005.07.956 · DOI
  39. Kalk, 1982, Thyroxine binding globulin and thyroid function tests in patients with hepatocellular carcinoma, Hepatology (Baltimore, Md)., 2, 72, 10.1002/hep.1840020112 · DOI
  40. Matsuoka, 2018, Heterotopic production of ceruloplasmin by lung adenocarcinoma is significantly correlated with prognosis, Lung Cancer (Amsterdam, Netherlands)., 118, 97, 10.1016/j.lungcan.2018.01.012 · DOI
  41. Dai, 2016, SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin, Nat. Commun., 7, 11996, 10.1038/ncomms11996 · DOI
  42. Lu, 2016, High serum haptoglobin level is associated with tumor progression and predicts poor prognosis in non-small cell lung cancer, Oncotarget, 7, 41758, 10.18632/oncotarget.9676 · DOI
  43. Zhao, 2007, Circulating haptoglobin is an independent prognostic factor in the sera of patients with epithelial ovarian cancer, Neoplasia (New York, NY)., 9, 1, 10.1593/neo.06619 · DOI
  44. Zhang, 2020, Saliva proteomic analysis reveals possible biomarkers of renal cell carcinoma, Open Chem., 18, 918, 10.1515/chem-2020-0048 · DOI
  45. Trowbridge, 1982, Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro, Proc. Natl. Acad. Sci. U. S. A., 79, 1175, 10.1073/pnas.79.4.1175 · DOI
  46. Rodríguez-Piñeiro, 2006, Differential expression of serum clusterin isoforms in colorectal cancer, Molecular & Cellular Proteomics: MCP., 5, 1647, 10.1074/mcp.M600143-MCP200 · DOI
  47. Palacios-Acedo, 2022, Platelet and cancer-cell interactions modulate cancer-associated thrombosis risk in different cancer types, Cancers, 14, 730, 10.3390/cancers14030730 · DOI
  48. Gajewska, 2022, Oxidative and antioxidative status expressed as OSI index and GSH/GSSG ratio in children with bone tumors after anticancer therapy completion, J. Clin. Med., 11, 1663, 10.3390/jcm11061663 · DOI
  49. Stewart, 2007, Dermcidin expression confers a survival advantage in prostate cancer cells subjected to oxidative stress or hypoxia, Prostate, 67, 1308, 10.1002/pros.20618 · DOI
  50. Menter, 2014, Platelets and cancer: a casual or causal relationship: revisited, Cancer Metastasis Rev., 33, 231, 10.1007/s10555-014-9498-0 · DOI
  51. Li, 2016, Platelets in cancer metastasis: to help the “villain” to do evil, Int. J. Cancer, 138, 2078, 10.1002/ijc.29847 · DOI
  52. Qu, 2009, Myeloid-specific expression of Api6/AIM/Sp alpha induces systemic inflammation and adenocarcinoma in the lung, J. Immunol., 182, 1648, 10.4049/jimmunol.182.3.1648 · DOI
  53. Aigner, 2019, STAT3 isoforms: alternative fates in cancer?, Cytokine, 118, 27, 10.1016/j.cyto.2018.07.014 · DOI
  54. Zoubeidi, 2010, Targeting the cytoprotective chaperone, clusterin, for treatment of advanced cancer, Clinical Cancer Research, 16, 1088, 10.1158/1078-0432.CCR-09-2917 · DOI
  55. Chou, 2009, Clusterin silencing in human lung adenocarcinoma cells induces a mesenchymal-to-epithelial transition through modulating the ERK/slug pathway, Cell. Signal., 21, 704, 10.1016/j.cellsig.2009.01.008 · DOI
  56. Shim, 2011, Clusterin induces matrix metalloproteinase-9 expression via ERK1/2 and PI3K/Akt/NF-κB pathways in monocytes/macrophages, J. Leukoc. Biol., 90, 761, 10.1189/jlb.0311110 · DOI
  57. Bosma, 2018, Prognostic factors for survival in Ewing sarcoma: a systematic review, Surg. Oncol., 27, 603, 10.1016/j.suronc.2018.07.016 · DOI

Cited by

Sorted by citations

See all 12

Metadata

Authors
Ezzeldin, S., Osama, A., Anwar, A. M., Mahgoub, S., Ahmed, E. A., Farid, N., Zamzam, M., El Ghoneimy, A., & Magdeldin, S.
Affiliations
  • Children Cancer Hospital (EG)
  • Suez Canal University (EG)
Corresponding author
Magdeldin, Sameh
Venue
Life Sciences
Publisher
Elsevier BV
Published
2023-12
Volume
334
Pages
122237
ISSN
0024-3205 (ISSN-L)
OpenAlex
W4388347112
Cited by
12
References
1
Citations by year
2026: 3 · 2025: 6 · 2024: 3
FWCI
2.22
Type
journal article
Language
en
Open access
closed
Locations
  • Life Sciences (publishedVersion)
  • PubMed (publishedVersion)
Funders
Egypt Cancer Network
Topics
  • Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
Keywords
Ewing sarcoma, childhood cancer, metastasis, prognostic factors, plasma proteome, circulating biomarkers, ceruloplasmin, immunoglobulins, clusterin, dermcidin, chemotherapy response, early detection
MeSH terms
Bone Neoplasms, Child, Humans, Prognosis, Sarcoma, Ewing, Proteome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Detection of early prognostic biomarkers for metastasis of Ewing's sarcoma in pediatric patients. https://app.cochat.ai/papers/10.1016/j.lfs.2023.122237
The paper
Ezzeldin, S., Osama, A., Anwar, A. M., Mahgoub, S., Ahmed, E. A., Farid, N., Zamzam, M., El Ghoneimy, A., & Magdeldin, S. (2023). Detection of early prognostic biomarkers for metastasis of Ewing's sarcoma in pediatric patients. Life Sciences. https://doi.org/10.1016/j.lfs.2023.122237