MicroRNA Biomarkers in Canine Diffuse Large B-Cell Lymphoma

Lymphoma is among the most common cancer in dogs. Diffuse large B-cell lymphoma (DLBCL) is the predominant type, accounting for up to half of all cases. Definitive diagnosis of DLBCL relies on cytologic evaluation with immunophenotyping, or histopathology and immunohistochemistry when needed. A rapid and specific molecular test aiding in the diagnosis could be beneficial. Noncoding microRNAs (miRNAs) are regulators of gene expression involved in a variety of cellular processes, including cell differentiation, cell cycle progression, and apoptosis. Not surprisingly, miRNA expression is aberrant in diseases such as cancers. Their high stability and abundance in tissues make them promising biomarkers for diagnosing and monitoring diseases. This study aimed to identify miRNA signatures of DLBCL to develop ancillary molecular diagnostic tools. miRNA was isolated from formalin-fixed, paraffin-embedded lymph node tissue from 22 DLBCL and 14 nonneoplastic controls. Relative gene expression of 8 tumor-regulating miRNAs was achieved by RT-qPCR (reverse transcriptase quantitative polymerase chain reaction). The results showed downregulation of the let-7 family of miRNAs and miR-155, whereas miR-34a was upregulated in DLBCL compared to the controls. We demonstrated that the combination of expression levels of miR-34a and let-7f or of let-7b and let-7f achieved 100% differentiation between DLBCL and controls. Furthermore, let-7f alone discriminated DLBCL from nonneoplastic tissue in 97% of cases. Our results represent one step forward in search of a rapid and accurate ancillary diagnostic test for DLBCL in dogs.