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Identification of non-invasive biomarkers for treatment response in neuroblastoma by circulating miRNA profiling

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Abstract
Introduction: An outstanding question in neuroblastoma treatment is whether clinically useful biomarkers of response to therapy can be identified. Biomarkers that allow monitoring of targeted drug pathway activation are highly desirable for the clinical follow-up of patients treated with such drugs. Minimally-invasive methods for patient follow-up, like measuring expression levels of miRNAs in serum, may be an elegant approach to obtain a higher specificity, sensitivity and lower handling time than other currently used biomarkers. Method: MYCN/ALKR1279Q transgenic mice were treated with crizotinib. Mice carrying orthotopic xenografts of SH-SY5Y cells were treated with RG7388 or temsirolimus. Serum samples of these mice were collected at different time points before, during and after treatment as well as matching end-point tumor material. Small RNA sequencing was optimized for low input and depleted for abundant non-relevant RNA sequences. Small RNA sequencing and whole miRNome RT-qPCR was performed to identify circulating miRNAs that are responsive to treatment or tumor cell engraftment. Results: We were able to observe expression changes for dozens up to one hundred circulating miRNAs, some of which had a >10 fold change in expression value. miRNAs showed differential expression both as a result of treatment and tumor cell engraftment. These include miRNAs with known roles in neuroblastoma tumor biology like the oncogenic miR-17-92 cluster. Moreover, for some miRNAs expression changes were found to be possibly drug-specific. Conclusion: These data encourage further investigation of circulating miRNAs as biomarkers for treatment response, also in a clinical setting.

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Chicago
Van Goethem, Alan, Nurten Yigit, Mythala Moreno-Smith, Celine Everaert, Olivier Delattre, Pieter Mestdagh, Saurabh Agarwal, et al. 2016. “Identification of Non-invasive Biomarkers for Treatment Response in Neuroblastoma by Circulating miRNA Profiling.” In Advances in Neuroblastoma Research, Congress Abstracts.
APA
Van Goethem, A., Yigit, N., Moreno-Smith, M., Everaert, C., Delattre, O., Mestdagh, P., Agarwal, S., et al. (2016). Identification of non-invasive biomarkers for treatment response in neuroblastoma by circulating miRNA profiling. Advances in Neuroblastoma Research, Congress abstracts. Presented at the Advances in Neuroblastoma Research 2016 (ANR 2016).
Vancouver
1.
Van Goethem A, Yigit N, Moreno-Smith M, Everaert C, Delattre O, Mestdagh P, et al. Identification of non-invasive biomarkers for treatment response in neuroblastoma by circulating miRNA profiling. Advances in Neuroblastoma Research, Congress abstracts. 2016.
MLA
Van Goethem, Alan, Nurten Yigit, Mythala Moreno-Smith, et al. “Identification of Non-invasive Biomarkers for Treatment Response in Neuroblastoma by Circulating miRNA Profiling.” Advances in Neuroblastoma Research, Congress Abstracts. 2016. Print.
@inproceedings{8071575,
  abstract     = {Introduction: An outstanding question in neuroblastoma treatment is whether clinically useful biomarkers of response to therapy can be identified. Biomarkers that allow monitoring of targeted drug pathway activation are highly desirable for the clinical follow-up of patients treated with such drugs. Minimally-invasive methods for patient follow-up, like measuring expression levels of miRNAs in serum, may be an elegant approach to obtain a higher specificity, sensitivity and lower handling time than other currently used biomarkers.
Method: MYCN/ALKR1279Q transgenic mice were treated with crizotinib. Mice carrying orthotopic xenografts of SH-SY5Y cells were treated with RG7388 or temsirolimus. Serum samples of these mice were collected at different time points before, during and after treatment as well as matching end-point tumor material. Small RNA sequencing was optimized for low input and depleted for abundant non-relevant RNA sequences. Small RNA sequencing and whole miRNome RT-qPCR was performed to identify circulating miRNAs that are responsive to treatment or tumor cell engraftment.
Results: We were able to observe expression changes for dozens up to one hundred circulating miRNAs, some of which had a {\textrangle}10 fold change in expression value. miRNAs showed differential expression both as a result of treatment and tumor cell engraftment. These include miRNAs with known roles in neuroblastoma tumor biology like the oncogenic miR-17-92 cluster. Moreover, for some miRNAs expression changes were found to be possibly drug-specific. 
Conclusion: These data encourage further investigation of circulating miRNAs as biomarkers for treatment response, also in a clinical setting.},
  author       = {Van Goethem, Alan and Yigit, Nurten and Moreno-Smith, Mythala and Everaert, Celine and Delattre, Olivier and Mestdagh, Pieter and Agarwal, Saurabh and Barbieri, Eveline and Janoueix-Lerosey, Isabelle and Shohet, Jason and Speleman, Franki and Van Maerken, Tom and Vandesompele, Jo},
  booktitle    = {Advances in Neuroblastoma Research, Congress abstracts},
  language     = {eng},
  location     = {Cairns, QLD, Australia},
  title        = {Identification of non-invasive biomarkers for treatment response in neuroblastoma by circulating miRNA profiling},
  year         = {2016},
}