Extracellular vesicle miRNA predict FDG-PET status in patients with classical Hodgkin Lymphoma
Metadatos
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John Wiley & Sons
Materia
Blood Extracellular vesicles Hodgkin lymphoma Liquid biopsy miRNA Response monitoring
Fecha
2021-07-15Referencia bibliográfica
Drees, E. E. E... [et al.] (2021). Extracellular vesicle miRNA predict FDG-PET status in patients with classical Hodgkin Lymphoma. Journal of Extracellular Vesicles, 10:e12121. [https://doi.org/10.1002/jev2.12121]
Patrocinador
KWF Kankerbestrijding KWF-5510; Cancer Center Amsterdam Foundation CCA-2013; Hodgkin Lymphoma MRD Foundation; Technologiestichting STWResumen
Minimally-invasive tools to assess tumour presence and burden may improve clinical
management. FDG-PET (metabolic) imaging is the current gold standard for interim
response assessment in patients with classical Hodgkin Lymphoma (cHL), but this
technique cannot be repeated frequently. Here we show that microRNAs (miRNA)
associated with tumour-secreted extracellular vesicles (EVs) in the circulation of cHL
patients may improve response assessment. Small RNA sequencing and qRT-PCR
reveal that the relative abundance of cHL-expressed miRNAs, miR-127-3p, miR-155-
5p, miR-21-5p, miR-24-3p and let-7a-5p is up to hundred-fold increased in plasma
EVs of cHL patients pre-treatmentwhen compared to completemetabolic responders
(CMR). Notably, in partial responders (PR) or treatment-refractory cases (n = 10)
the EV-miRNA levels remain elevated. In comparison, tumour specific copy number
variations (CNV) were detected in cell-free DNA of 8 out of 10 newly diagnosed
cHL patients but not in patients with PR. Combining EV-miR-127-3p and/or EV-let-
7a-5p levels, with serum TARC (a validated protein cHL biomarker), increases the
accuracy for predicting PET-status (n = 129) to an area under the curve of 0.93 (CI:
0.87-0.99), 93.5% sensitivity, 83.8/85.0% specificity and a negative predictive value
of 96%. Thus the level of tumour-associated miRNAs in plasma EVs is predictive
of metabolic tumour activity in cHL patients. Our findings suggest that plasma EV-miRNA are useful for detection of small residual lesions and may be applied as
serial response prediction tool.