Exploratory screening for miRNA biomarkers in canine multicentric lymphoma.

Objective: Micro-RNAs (miRNA, small non-coding RNAs) are pivotal in gene regulation fine tuning and their aberrant expression is expected in cancer. miRNAs might serve as diagnostic biomarkers and assist predicting therapeutic response and clinical outcome. Aim of this study was to investigate dysregulated miRNAs in lymphomatous lymph node tissues in comparison to normal lymph node material and peripheral blood mononuclear cells (PBMC) from healthy control dogs. Differences in miRNA expression between four lymphoma entities were assessed. Methods: A panel of 89 canine target miRNAs were profiled by a customized PCR array. Quantification was performed by quantitative real time PCR and relative expression was determined by the delta-delta Ct method using the GeneGlobe Data Analysis Center (Qiagen, www.qiagen.com). Fold changes were evaluated by student’s t-test and p-values less than 0.05 were considered significant. Results: In total, 85 out of 89 miRNAs were successfully amplified and many were differently expressed in the lymphoma entities. In the 14 diffuse large B-cell lymphoma (DLBCL) patients, 28 miRNAs were significantly dysregulated in lymph node material and 24 miRNAs showed significant aberrations in PBMC. The six peripheral T-cell lymphoma (PTCL) samples showed 24 (lymph node) and 25 (PBMC) dysregulated miRNAs when compared to the healthy controls. A combined analysis of DLBCL and PTCL samples revealed seven shared and 19 differently expressed miRNAs. Conclusions: The miRNA-17-92 cluster, miRNA-34a, miRNA-150, and miRNA-181-family might serve as biomarkers in canine T- and B-cell lymphoma. A panel of 26 significantly dysregulated miRNAs will be applied to confirm and validate these miRNAs together with those with unknown function and still missing literature record.

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