Micro-RNA Profiling for the Diagnosis and Prognosis of Canine Multicentric Lymphoma

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Gow, William R
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University of Guelph

MicroRNAs (miRs) are small non-coding RNAs (18-22 nucleotides in length) that have important roles in mRNA translation and hence expression of proteins. Dysregulated miR expression has been shown in people with lymphoma (Burkitt lymphoma and diffuse large B cell lymphoma (DLBCL) and childhood acute lymphoblastic leukemia. More importantly, miRs have been detected in serum samples in human patients with DLBCL and have been correlated with response to rituximab-cyclophosphamide (C), doxorubicin (H), vincristine (O) and prednisone (P) (CHOP) therapy and relapse-free survival times. There have been no studies looking at miRs in serum or plasma samples in dogs with lymphoma. The aim of our studies was to profile the miR expression in plasma of healthy control dogs, and to compare to dogs with B cell and T cell lymphoma. We also compared miR expression with clinical outcomes in B cell lymphoma patients. We initially examined 277 miRs previously shown to exist in various canine tissues, which were then reduced to a smaller array of 45 miRs, assayed using a microarray plate system and quantitative real time reverse transcription PCR. Among the 277 miRs there were significant increases in expression of 20 miRs in the B cell group and of 7 miRs in the T cell group. Furthermore, 17 miRs were in common between the B cell and T cell lymphoma groups. The smaller array showed increases in expression of 12 different miRs in B cell lymphoma patients and one miR in T cell lymphoma patients when compared to controls. In addition, there were 6 miRs with significantly decreased expression when patients in non-remission (patients that never responded to therapy and those that relapsed) were compared to those patients that achieved remission. MicroRNA expression was followed over time during CHOP therapy; one miR (miR-130b) showed significantly increased expression at week 3 of chemotherapy in patients that did not respond to CHOP therapy when compared to patients in remission and relapse. When survival greater than 365 days was examined, there were no significant differences in miR expression. Kaplan-Meier survival curves with high and low expressing miRs were also not significantly different. This study highlights miRs, that with further validation, could be used as minimally invasive biomarkers with diagnostic and predictive value in canine lymphoma patients, and could be a step towards a degree of personalised patient medicine in veterinary cancer patients.

biomarker, microRNA, micro-RNA, lymphoma, canine lymphoma, chemotherapy, plasma