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

Marius Rohde,1,* Vijay Kumar Singh,1,* Andrea Wolfermann,1 Birgit Burkhardt,2 Claudia Blattmann,3 Daniel Steinbach,4 Dominik T Schneider,5 Martin Ebinger,6 Britta Maecker-Kolhoff,7 Matthias Braun,1 Lars Kurch,8,9 Christine Mauz-Körholz,1,10 Dieter Körholz1 1Department of Pediatric Oncology, Hematology and Immunodeficiencies, Justus-Liebig-University, Giessen, Germany; 2Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany; 3Pediatric Oncology, Hematology, Immunology, Klinikum Stuttgart-Olgahospital Stuttgart Cancer Center, Stuttgart, Germany; 4Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany; 5Clinic of Pediatrics, Dortmund Municipal Hospital, University Witten/Herdecke, Dortmund, Germany; 6Department of Paediatric Hematology, Oncology, Gastroenterology, Nephrology and Rheumatology, University Children’s Hospital Tübingen, Tübingen, Germany; 7Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; 8Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany; 9Department of Anesthesiology and Operative Intensive Care, University Hospital Halle (Saale), Halle (Saale), Germany; 10Medical Faculty, Martin-Luther University of Halle-Wittenberg, Halle, Germany*These authors contributed equally to this workCorrespondence: Marius Rohde, Department of Pediatric Oncology, Hematology and Immunodeficiencies, Justus-Liebig-University, Feulgenstraße 10-12, Giessen, 35392, Germany, Tel +49 641 985 43421, Fax +49 641 985 43429, Email [email protected]: 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