Gene Expression Analysis of (Paired) Primary and Relapsed Wilms Tumor Samples to Unravel the Underlying Factors Driving Tumor Recurrence
ABSTRACT Purpose We aimed to unravel underlying factors driving Wilms tumor (WT) recurrence and to build a prediction model for recurrence based on gene expression data of (paired) primary and relapsed WT samples. Experimental Design Gene expression levels from seven paired primary and relapsed WT s...
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| Format: | Article |
| Language: | English |
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Wiley
2025-06-01
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| Series: | Cancer Medicine |
| Online Access: | https://doi.org/10.1002/cam4.70969 |
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| author | Alissa Groenendijk Jarno Drost Annelies M. C. Mavinkurve‐Groothuis Martine vanGrotel Geert O. Janssens Annemieke S. Littooij Alida F. W. van derSteeg Marry M. van denHeuvel‐Eibrink Lennart Kester Ronald R. deKrijger |
| author_facet | Alissa Groenendijk Jarno Drost Annelies M. C. Mavinkurve‐Groothuis Martine vanGrotel Geert O. Janssens Annemieke S. Littooij Alida F. W. van derSteeg Marry M. van denHeuvel‐Eibrink Lennart Kester Ronald R. deKrijger |
| author_sort | Alissa Groenendijk |
| collection | DOAJ |
| description | ABSTRACT Purpose We aimed to unravel underlying factors driving Wilms tumor (WT) recurrence and to build a prediction model for recurrence based on gene expression data of (paired) primary and relapsed WT samples. Experimental Design Gene expression levels from seven paired primary and relapsed WT samples from patients treated in the Princess Máxima Center were compared among each other, as well as to matched primary WT samples of patients without recurrence (controls). The differential gene expression analysis results were run through ToppGene for functional enrichment. We built a 10‐fold ridge regression model to predict relapse based on gene expression levels of the seven primary cases and all other available primary WT controls (n = 42). Results The comparison of primary WT and paired relapses showed downregulation of genes involved in immune regulation among relapses and upregulation of cancer stem cell (CSC) regulation genes. Comparing these primary WT samples to matched controls, we observed that downregulated genes in primary samples of relapsed patients were related to stromal cells and muscle development, and upregulated genes were associated with CSCs. The prediction model revealed a sensitivity of 57.14% (95% CI: 14.29%–85.71%) and a specificity of 92.86% (95% CI: 83.33%–100%) when predicting WT relapse. Conclusion The CSC pool could play a role in relapse through immune regulation and tumor propagation. Differentiation of CSCs into mesenchymal cells might attenuate the risk of relapse. Our prediction model might aid in selecting patients with an increased risk of relapse at primary diagnosis when externally validated. |
| format | Article |
| id | doaj-art-4ed7f58ce83e40e5b8a693f025a3d2a3 |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-4ed7f58ce83e40e5b8a693f025a3d2a32025-08-20T03:21:19ZengWileyCancer Medicine2045-76342025-06-011411n/an/a10.1002/cam4.70969Gene Expression Analysis of (Paired) Primary and Relapsed Wilms Tumor Samples to Unravel the Underlying Factors Driving Tumor RecurrenceAlissa Groenendijk0Jarno Drost1Annelies M. C. Mavinkurve‐Groothuis2Martine vanGrotel3Geert O. Janssens4Annemieke S. Littooij5Alida F. W. van derSteeg6Marry M. van denHeuvel‐Eibrink7Lennart Kester8Ronald R. deKrijger9Princess Máxima Center for Pediatric Oncology Utrecht the NetherlandsPrincess Máxima Center for Pediatric Oncology Utrecht the NetherlandsPrincess Máxima Center for Pediatric Oncology Utrecht the NetherlandsPrincess Máxima Center for Pediatric Oncology Utrecht the NetherlandsPrincess Máxima Center for Pediatric Oncology Utrecht the NetherlandsPrincess Máxima Center for Pediatric Oncology Utrecht the NetherlandsPrincess Máxima Center for Pediatric Oncology Utrecht the NetherlandsPrincess Máxima Center for Pediatric Oncology Utrecht the NetherlandsPrincess Máxima Center for Pediatric Oncology Utrecht the NetherlandsPrincess Máxima Center for Pediatric Oncology Utrecht the NetherlandsABSTRACT Purpose We aimed to unravel underlying factors driving Wilms tumor (WT) recurrence and to build a prediction model for recurrence based on gene expression data of (paired) primary and relapsed WT samples. Experimental Design Gene expression levels from seven paired primary and relapsed WT samples from patients treated in the Princess Máxima Center were compared among each other, as well as to matched primary WT samples of patients without recurrence (controls). The differential gene expression analysis results were run through ToppGene for functional enrichment. We built a 10‐fold ridge regression model to predict relapse based on gene expression levels of the seven primary cases and all other available primary WT controls (n = 42). Results The comparison of primary WT and paired relapses showed downregulation of genes involved in immune regulation among relapses and upregulation of cancer stem cell (CSC) regulation genes. Comparing these primary WT samples to matched controls, we observed that downregulated genes in primary samples of relapsed patients were related to stromal cells and muscle development, and upregulated genes were associated with CSCs. The prediction model revealed a sensitivity of 57.14% (95% CI: 14.29%–85.71%) and a specificity of 92.86% (95% CI: 83.33%–100%) when predicting WT relapse. Conclusion The CSC pool could play a role in relapse through immune regulation and tumor propagation. Differentiation of CSCs into mesenchymal cells might attenuate the risk of relapse. Our prediction model might aid in selecting patients with an increased risk of relapse at primary diagnosis when externally validated.https://doi.org/10.1002/cam4.70969 |
| spellingShingle | Alissa Groenendijk Jarno Drost Annelies M. C. Mavinkurve‐Groothuis Martine vanGrotel Geert O. Janssens Annemieke S. Littooij Alida F. W. van derSteeg Marry M. van denHeuvel‐Eibrink Lennart Kester Ronald R. deKrijger Gene Expression Analysis of (Paired) Primary and Relapsed Wilms Tumor Samples to Unravel the Underlying Factors Driving Tumor Recurrence Cancer Medicine |
| title | Gene Expression Analysis of (Paired) Primary and Relapsed Wilms Tumor Samples to Unravel the Underlying Factors Driving Tumor Recurrence |
| title_full | Gene Expression Analysis of (Paired) Primary and Relapsed Wilms Tumor Samples to Unravel the Underlying Factors Driving Tumor Recurrence |
| title_fullStr | Gene Expression Analysis of (Paired) Primary and Relapsed Wilms Tumor Samples to Unravel the Underlying Factors Driving Tumor Recurrence |
| title_full_unstemmed | Gene Expression Analysis of (Paired) Primary and Relapsed Wilms Tumor Samples to Unravel the Underlying Factors Driving Tumor Recurrence |
| title_short | Gene Expression Analysis of (Paired) Primary and Relapsed Wilms Tumor Samples to Unravel the Underlying Factors Driving Tumor Recurrence |
| title_sort | gene expression analysis of paired primary and relapsed wilms tumor samples to unravel the underlying factors driving tumor recurrence |
| url | https://doi.org/10.1002/cam4.70969 |
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