Circulating miR-148a-3p Correlates with Inadequate Induction Response in Pediatric Hodgkin Lymphoma

Abstract: Pediatric Hodgkin lymphoma (HL) is highly curable, and reducing the treatment intensity in patients who respond well to induction therapy is a key strategy for minimizing long-term adverse effects. Biomarkers that identify good responders at diagnosis would enable further de-escalation of the treatment. Circulating microRNAs (miRNAs) have shown promise as noninvasive indicators of therapeutic response in hematological cancers, yet their association with early metabolic response on quantitative 18F-Fluorodeoxyglucose-Positron Emission Tomography (18F-FDG-PET) in pediatric HL has not been defined. Here, we investigated the potential of circulating miRNAs to predict the response to induction therapy in pediatric HL. Small RNA sequencing of serum samples from 35 patients revealed 24 Hodgkin lymphoma–associated miRNAs that were differentially expressed between adequate and inadequate responders. Subsequent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) validation demonstrated significantly elevated miR‑148a‑3p levels at diagnosis in inadequate responders to induction therapy than in adequate responders (p=0.009). These results indicate that circulating miR‑148a‑3p may enhance current predictive approaches by identifying high‑risk patients less likely to achieve rapid metabolic remission. Keywords: pediatric cancer, classical Hodgkin lymphoma, microRNA, circulating microRNA, serum, biomarker, early response assessment quantitative positron emission tomography