Classification and Prognostication of B-Cell and T-Cell Multicentric Lymphoma in Dogs Using Serum MicroRNAs

Canine multicentric lymphoma is a common malignancy in dogs. It often responds well to initial chemotherapy but frequently relapses and has a poor response to subsequent treatment. B-cell (BCL) and T-cell (TCL) lymphomas differ in both their prognoses and chemotherapeutic treatment protocols. Currently, immunophenotyping can be costly and can only be performed on specific high-quality samples. MicroRNAs (miRNAs) are small molecules present in blood and tissues and are dysregulated in both human and canine lymphoma. We investigated 59 miRNAs by RT-qPCR to establish a serum miRNA profile in dogs with B-cell and T-cell multicentric lymphoma. Multiple miRNA pruned decision tree models were used to classify BCL and TCL cases from each other and controls, and to predict prognosis in BCL cases receiving standard CHOP chemotherapy. Six individual miRNAs were differentially expressed in serum between BCL and controls, and three were differentially expressed between BCL and TCL. A three-miRNA model (miR-155-5p, miR-1 and miR-181b) could differentiate between BCL, TCL and control samples with an accuracy of 83.02%. A three-miRNA model (miR-125b-5p, miR-350 and let-7b-5p) in BCL samples separated the cases into four groups with hazard ratios ranging from 0.44 to 3.5 for overall survival. This study established a serum miRNA profile for both BCL and TCL and demonstrated the utility of multiple serum miRNA models to assist in the diagnosis of lymphoma and BCL prognostication.