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| Status |
Public on Sep 04, 2024 |
| Title |
Quantification of tumour-infiltrating immune cells through deconvolution of DNA methylation data in Ewing sarcomas |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Ewing Sarcomas (EWS, OMIM#612219) presents a major challenge in pediatric oncology due to its aggressive nature and poor prognosis, particularly in metastatic cases. Genetic fusions involving the EWSR1 gene and ETS family transcription factors are common in EWS, though other rarer fusions have also been identified. Current standard techniques like immunohistochemistry have failed to fully characterize the immune tumor microenvironment of EWS, hindering insights into tumor development and treatment strategies. Recent efforts apply gene expression datasets to quantify tumor-infiltrating immune cells in EWS. Similar deconvolution techniques can be also applied to DNA methylation (DNAm) arrays, which are much more stable compared to RNA-based methods. This study aims to characterize immune cell infiltration in EWS using DNAm array data. We collected 32 EWS samples from 32 consecutive patients referred to Bambino Gesù Children’s Hospital. DNAm analysis was performed by EPIC arrays; data loading, normalization, deconvolution and survival analysis were then performed in R programming environment. We observed a higher content of dendritic cells and longer overall survival in samples with EWSR1::FLI1 translocation compared to samples with rarer fusions. Moreover, T-memory lymphocytes and monocytes emerged as a significant predictor of overall survival. This study underscores the potential of DNAm arrays in providing robust insights into EWS immune profiles, offering a promising avenue for future research. Further investigations with larger cohorts are warranted to validate these findings and explore additional immune cell types influencing EWS outcomes.
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| Overall design |
We performed immune cell content deconvolution of the normalized DNA methylation data through package MethylResolver. Then, we used two-tailed heteroschedastic Student’s T-test to evaluate the statistical significance of differences in immune cell content between sample groups (canonical vs. non-canonical), and Kaplan-Meier analysis to assess the relationship between immune cell content and overall survival.
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| Web link |
https://doi.org/10.3389/freae.2024.1427399
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| Contributor(s) |
Miele E |
| Citation missing |
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| Submission date |
Aug 29, 2024 |
| Last update date |
Dec 04, 2024 |
| Contact name |
Evelina Miele |
| E-mail(s) |
evelina.miele@opbg.net
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| Organization name |
Ospedale Pediatrico Bambino Gesù
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| Department |
Oncoematologia
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| Street address |
Piazza di Sant'Onofrio 4
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| City |
Rome |
| ZIP/Postal code |
00165 |
| Country |
Italy |
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| Platforms (2) |
| GPL21145 |
Infinium MethylationEPIC |
| GPL33022 |
Illumina Infinium MethylationEPIC version 2 |
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