Salivary miR-21 is a potential biomarker for canine mast cell tumors

Abstract

MicroRNAs (miRNAs) are a class of noncoding RNA molecules playing a crucial role in tumor modulation targeting mRNA. This study aimed to validate the diagnostic potential of a panel of 3 miRNAs previously identified in canine mast cell tumors (MCTs), miR-21, miR-379, and miR-885, as markers of lymph node involvement in terms of histological absence (nonmetastatic: HN0; premetastatic: HN1) and presence (early-metastatic: HN2; overt-metastatic: HN3) of metastasis, in the saliva of mast cell tumor (MCT)-affected dogs by quantitative polymerase chain reaction (PCR). Forty-seven saliva samples were analyzed: 36 from MCT-affected dogs (12 subcutaneous [3 HN0-1 and 9 HN2-3] and 24 cutaneous [9 HN0-1 and 15 HN2-3—MCT]) and 11 from healthy dogs. MCT-group effects were investigated using analysis of variance (ANOVA). The origin of the tumor affected the expression of salivary miR-21 ( P = .011) with an increase in cases with subcutaneous MCTs compared with the healthy group ( P = .0005) and those with cutaneous MCTs ( P = .004). Salivary miR-21 was higher in the HN2-3 class compared with the healthy group ( P = .004). Salivary miR-885 was not affected by the presence of MCT, while miR-379 was not detected in saliva. The diagnostic potential of salivary miR-21 in discriminating MCT-affected dogs from the healthy group (AUC = 0.8917), cutaneous from subcutaneous (AUC = 0.8111), and subcutaneous HN0-1 (AUC = 0.7250) and HN2-3 (AUC = 0.9750) classes from healthy samples was demonstrated by receiver operating characteristic curve analysis. Overall, salivary miR-21 was identified as a promising tool, representing a novel approach to detecting MCT-associated epigenetic alterations in a minimally invasive manner.

Plasma small extracellular vesicles from dogs affected by cutaneous mast cell tumors deliver high levels of miR-21-5p

“…In the MCT group, dogs with a cytological diagnosis of MCT, that were preoperatively staged negative for distant metastases ( 34 ) and underwent wide margins surgical excision of the MCT and biopsy of the sentinel lymph node(s) (SLN), without any medical treatment for at least 14 days before surgery, were included ( 35 , 36 ). Histopathology was performed on both primary tumor and SLN samples as previously reported ( 27 ). The MCTs were grouped based on SLN involvement in two classes: non-metastatic/pre-metastatic (HN0-1 class) and early-metastatic/overt-metastatic (HN2-3 class) ( 8 ).…”

“…The miRNAs profile of canine MCT has been previously characterized in formalin-fixed paraffin-embedded samples pointing out that a panel of three miRNAs, miR-21-5p, miR-379, and miR-885, have a good efficiency in discriminating healthy and MCT affected dogs, and MCT affected dogs with and without nodal metastasis, suggesting an epigenetic role in tumor progression ( 26 ). Recently, miR-21-5p has been identified as a potential biomarker in the saliva of MCT-affected dogs ( 27 ). No data on plasma circulating miR-21-5p in MCT-affected dogs have been reported so far.…”

Genetic Changes in Mastocytes and Their Significance in Mast Cell Tumor Prognosis and Treatment

“…The panel of three miRNAs, including miR-21-5p, miR-379, and miR-885, has a good efficiency in discriminating healthy and MCT-affected dogs, as well as MCT-affected dogs with and without nodal metastasis [279]. Moreover, in the saliva of dogs affected by MCT, miR-21-5p has been identified as a potential negative prognostic factor [280]. MiR-21-5p is one of the miRNAs described as upregulated in canine MCT [279].…”