MicroRNAs in serum and tissue can differentiate splenic hemangiosarcoma from other splenic masses in dogs

Splenic masses are common in dogs and vary dramatically in their clinical behavior. Clinically, and even with histology, it can be challenging to differentiate between benign and malignant splenic masses. Hemangiosarcoma (HSA), the most common malignancy of the spleen, is a very aggressive tumor with a poor prognosis. We hypothesize that microRNAs (miRNAs) in mass tissue and serum can differentiate between HSA and other splenic masses. Fifty-nine miRNAs were investigated by reverse-transcription followed by real-time quantitative polymerase chain reaction (RT-qPCR) in serum and/or tissue from dogs with HSAs (serum n = 24 and tissue n = 17; postsplenectomy serum n = 11), lymphomas (serum n = 8 and tissue n = 11), nonangiomatous nonlymphomatous sarcomas (serum n = 6 and tissue n = 10), histiocytic sarcomas (tissue n = 4), benign splenic masses (myelolipomas, nodular hyperplasia, and hematomas; total serum n = 21 and total tissue n = 35), and normal dogs (serum n = 14 and tissue n = 7). Numerous miRNAs were differentially expressed in serum and tissue of HSA cases compared to those with other splenic masses or normal spleens. In serum, our 5-miRNA model (miR-135a-5p, miR-10a, miR-450b, miR-152-3p, and miR-126-5p) accurately classified 100% (24/24) of dogs with HSA from normal dogs and those with a benign splenic mass (recall = 1 for HSA). The overall accuracy of the model was 86%. In HSA and benign splenic mass tissues, our 3-miRNA model (miR-126-5p, miR-502-3p, and miR-452-5p) accurately classified 96% of the cases. This study demonstrates the utility of miRNA models in serum and tissue for screening and diagnosis of HSA in dogs. Future studies include the evaluation of prospective and prediagnosis serum samples.