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Potential diagnostic and prognostic biomarkers of pediatric Burkitt lymphoma identified through miRNA expression
Can Küçük1,2, Esra Esmeray Sönmez3,4, Tevfik Hatipoğlu3,4
1Department of Medical Biology, Faculty of Medicine, Dokuz Eylül University, İzmir, Türkiye. can.kucuk@deu.edu.tr.
Insights
MicroRNAs (miRNAs) in pediatric Burkitt lymphoma (pBL) tumor tissue and plasma show potential as diagnostic and prognostic biomarkers. This study identified specific miRNAs that can improve early detection and patient outcome prediction in pBL.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Pediatric Burkitt lymphoma (pBL) is a rapidly progressing non-Hodgkin lymphoma requiring timely diagnosis and treatment.
- The diagnostic and prognostic roles of microRNAs (miRNAs) in pBL remain incompletely understood.
Purpose of the Study:
- To identify differentially expressed miRNAs (DE miRNAs) in tumor tissues and plasma of pediatric Burkitt lymphoma (pBL) patients.
- To evaluate the diagnostic and prognostic potential of these DE miRNAs for pBL.
Main Methods:
- MicroRNA sequencing (miRNA-Seq) was performed on tumor tissues and plasma from diagnostic pBL cases.
- Receiver operating characteristic (ROC) analyses assessed the diagnostic accuracy of miRNA concentrations.
- Log-rank tests evaluated survival differences associated with DE miRNAs, with cross-validation using qRT-PCR.
Main Results:
- Circulating cell-free miRNAs were significantly higher in pBL patients compared to controls.
- DE miRNAs in pBL tumors were enriched in cancer-associated pathways, with several showing high diagnostic potential.
- Plasma miRNAs, particularly exosomal miRNAs, demonstrated diagnostic capability for pBL, with triple combinations showing enhanced potential. DE miRNAs in tumor tissue predicted overall survival.
Conclusions:
- DE miRNAs in both tumor tissue and plasma of pBL patients hold significant potential for improving diagnosis and prognosis.
- This study provides the first miRNA-Seq analysis of treatment-naive pBL, identifying novel diagnostic and prognostic miRNA biomarkers.
- These findings could enhance current clinical practices for pBL diagnosis and prognostication.
Background:
Pediatric Burkitt lymphoma (pBL) is the most common non-Hodgkin lymphoma in children. These patients require prompt diagnosis and initiation of therapy due to rapid tumor growth. The roles of tumor tissue and circulating microRNAs (miRNAs) in the diagnosis or prognostication have not been fully elucidated in pBLs.
Methods:
Differentially expressed (DE) miRNAs were identified with microRNA sequencing (miRNA-Seq) in tumor tissues and plasma of diagnostic pBLs. The diagnostic potential of total miRNA concentrations and overexpressed miRNAs were evaluated through receiver operating characteristic (ROC) analyses. Log-rank test was employed to evaluate survival differences associated with DE miRNAs. Selected miRNA expressions were cross-validated with quantitative reverse transcription PCR (qRT-PCR).
Results:
Total circulating cell-free miRNAs were higher in pBL cases compared to controls. Cancer-associated pathways were enriched among miRNAs differentially expressed in pBL tumor tissues. Several upregulated miRNAs in pBL tumors demonstrated high diagnostic potential. Similarly, ROC analysis of overexpressed plasma miRNAs revealed circulating cell-free or exosomal miRNAs that can distinguish pBLs from control cases. Indeed, integrative analysis of overexpressed circulating exosomal miRNAs showed an enhanced diagnostic potential for certain triple combinations. Kaplan-Meier analyses of DE miRNAs in tumor tissues identified miRNAs predicting overall survival.
Conclusions:
Differentially expressed miRNAs in tumor tissue and plasma of pBL have the potential to improve diagnosis and prognosis.
Impact:
Differentially expressed miRNAs in treatment-naive pediatric Burkitt lymphoma cases have diagnostic or prognostic biomarker potential. This is the first study that applied miRNA-Seq on treatment-naive pediatric Burkitt lymphoma cases for identification of differentially expressed miRNAs both in tumor tissue and plasma samples with diagnostic potential. Through systematic analysis of differentially expressed miRNAs, tumor tissue miRNAs associated with the overall survival of pBLs have been discovered. The clinically significant, differentially expressed miRNAs identified in pediatric Burkitt lymphoma cases can potentially improve the current tissue-based or non-invasive clinical practice in terms of diagnosis or prognostication.
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