Advanced search
1 file | 1.37 MB

Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time

Bert Dhondt (UGent) , Elise De Bleser (UGent) , Tom Claeys, Sarah Buelens (UGent) , Nicolaas Lumen (UGent) , Jo Vandesompele (UGent) , Anneleen Beckers, Valerie Fonteyne (UGent) , Kim Van der Eecken (UGent) , Aurélie De Bruycker (UGent) , et al.
Author
Organization
Abstract
Purpose Patients with oligometastatic prostate cancer (PC) may beneft from metastasis-directed therapy (MDT), delaying disease progression and the start of palliative systemic treatment. However, a signifcant proportion of oligometastatic PC patients progress to polymetastatic PC within a year following MDT, suggesting an underestimation of the metastatic load by current staging modalities. Molecular markers could help to identify true oligometastatic patients eligible for MDT. Methods Patients with asymptomatic biochemical recurrence following primary PC treatment were classifed as oligo- or polymetastatic based on 18F-choline PET/CT imaging. Oligometastatic patients had up to three metastases at baseline and did not progress to more than three lesions following MDT or surveillance within 1 year of diagnosis of metastases. Polymetastatic patients had>3 metastases at baseline or developed>3 metastases within 1 year following imaging. A model aiming to prospectively distinguish oligo- and polymetastatic PC patients was trained using clinicopathological parameters and serum-derived microRNA expression profles from a discovery cohort of 20 oligometastatic and 20 polymetastatic PC patients. To confrm the models predictive performance, it was applied on biomarker data obtained from an independent validation cohort of 44 patients with oligometastatic and 39 patients with polymetastatic disease. Results Oligometastatic PC patients had a more favorable prognosis compared to polymetastatic ones, as defned by a signifcantly longer median CRPC-free survival (not reached versus 38 months; 95% confdence interval 31–45 months with P<0.001). Despite the good performance of a predictive model trained on the discovery cohort, with an AUC of 0.833 (0.693–0.973; 95% CI) and a sensitivity of 0.894 (0.714–1.000; 95% CI) for oligometastatic disease, none of the miRNA targets were found to be diferentially expressed between oligo- and polymetastatic PC patients in the signature validation cohort. The multivariate model had an AUC of 0.393 (0.534 after cross-validation) and therefore, no predictive ability. Conclusions Although PC patients with oligometastatic disease had a more favorable prognosis, no serum-derived biomarkers allowing for prospective discrimination of oligo- and polymetastatic prostate cancer patients could be identifed.
Keywords
Urology

Downloads

  • Dhondt2018 Article DiscoveryAndValidationOfASerum.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 1.37 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Dhondt, Bert, Elise De Bleser, Tom Claeys, Sarah Buelens, Nicolaas Lumen, Jo Vandesompele, Anneleen Beckers, et al. 2018. “Discovery and Validation of a Serum microRNA Signature to Characterize Oligo- and Polymetastatic Prostate Cancer: Not Ready for Prime Time.” World Journal of Urology.
APA
Dhondt, B., De Bleser, E., Claeys, T., Buelens, S., Lumen, N., Vandesompele, J., Beckers, A., et al. (2018). Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time. World Journal of Urology.
Vancouver
1.
Dhondt B, De Bleser E, Claeys T, Buelens S, Lumen N, Vandesompele J, et al. Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time. World Journal of Urology. Springer Nature; 2018;
MLA
Dhondt, Bert, Elise De Bleser, Tom Claeys, et al. “Discovery and Validation of a Serum microRNA Signature to Characterize Oligo- and Polymetastatic Prostate Cancer: Not Ready for Prime Time.” World Journal of Urology (2018): n. pag. Print.
@article{8586484,
  abstract     = {Purpose 
Patients with oligometastatic prostate cancer (PC) may beneft from metastasis-directed therapy (MDT), delaying
disease progression and the start of palliative systemic treatment. However, a signifcant proportion of oligometastatic PC patients progress to polymetastatic PC within a year following MDT, suggesting an underestimation of the metastatic load by current staging modalities. Molecular markers could help to identify true oligometastatic patients eligible for MDT.
Methods 
Patients with asymptomatic biochemical recurrence following primary PC treatment were classifed as oligo- or polymetastatic based on 18F-choline PET/CT imaging. Oligometastatic patients had up to three metastases at baseline and did not progress to more than three lesions following MDT or surveillance within 1 year of diagnosis of metastases. Polymetastatic patients had{\textrangle}3 metastases at baseline or developed{\textrangle}3 metastases within 1 year following imaging. A model aiming to prospectively distinguish oligo- and polymetastatic PC patients was trained using clinicopathological parameters and serum-derived microRNA expression profles from a discovery cohort of 20 oligometastatic and 20 polymetastatic PC patients. To confrm the models predictive performance, it was applied on biomarker data obtained from an independent validation cohort of 44 patients with oligometastatic and 39 patients with polymetastatic disease.
Results 
Oligometastatic PC patients had a more favorable prognosis compared to polymetastatic ones, as defned by a signifcantly longer median CRPC-free survival (not reached versus 38 months; 95\% confdence interval 31--45 months with P{\textlangle}0.001). Despite the good performance of a predictive model trained on the discovery cohort, with an AUC of 0.833 (0.693--0.973; 95\% CI) and a sensitivity of 0.894 (0.714--1.000; 95\% CI) for oligometastatic disease, none of the miRNA targets were found to be diferentially expressed between oligo- and polymetastatic PC patients in the signature validation cohort. The multivariate model had an AUC of 0.393 (0.534 after cross-validation) and therefore, no predictive ability.
Conclusions 
Although PC patients with oligometastatic disease had a more favorable prognosis, no serum-derived biomarkers
allowing for prospective discrimination of oligo- and polymetastatic prostate cancer patients could be identifed.},
  author       = {Dhondt, Bert and De Bleser, Elise and Claeys, Tom and Buelens, Sarah and Lumen, Nicolaas and Vandesompele, Jo and Beckers, Anneleen and Fonteyne, Valerie and Van der Eecken, Kim and De Bruycker, Aur{\'e}lie and Paul, J{\'e}r{\^o}me and Gramme, Pierre and Ost, Piet},
  issn         = {0724-4983},
  journal      = {World Journal of Urology},
  language     = {eng},
  publisher    = {Springer Nature},
  title        = {Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time},
  url          = {http://dx.doi.org/10.1007/s00345-018-2609-8},
  year         = {2018},
}

Altmetric
View in Altmetric