A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs

Splenic masses are common in older dogs and may be malignant, benign, or non-neoplastic; yet diagnosis preceding splenectomy and histopathology remains elusive. MicroRNAs (miRNAs) are 18-25 nucleotide, single stranded, non-coding RNAs that play a role in post-transcriptional regulation. MicroRNAs in tumor samples have been used to diagnose tumors, provide prognostic information, and aid in targeted treatments in human medicine, but have not been extensively evaluated in veterinary medicine. The objective of this study was to determine differential expression of microRNAs (miRNAs) between canine splenic hemangiosarcoma, canine splenic nodular hyperplasia, and normal canine spleens by use of RNA-sequencing. Eighteen miRNAs were found to be significantly differentially expressed between hemangiosarcoma and nodular hyperplasia only. The five of these with the largest fold change were mir-193a, mir-450a, mir-503, mir-542, and mir-876. Four miRNA were significantly differentially expressed between hemangiosarcoma and nodular hyperplasia and also hemangiosarcoma and normal spleen (mir-126, mir-150, mir-203, and mir-452). Findings of this study show that miRNA expression profiles are different between canine splenic hemangiosarcoma, nodular hyperplasia, and normal spleens. This is a preliminary study with findings of clinical relevance, as masses of the spleen cannot be diagnosed pre-operatively in most cases. Canine splenic masses are relatively common, and validation these findings is warranted for potential use as a diagnostic test. Overall design: A total of fifteen samples total were analyzed for miRNA expression. There were 3 experimental condition with 5 replicates in each group.

老年犬脾脏肿物较为常见，其性质可分为恶性、良性与非肿瘤性三类；但在实施脾切除术并开展组织病理学检查前，仍难以实现明确诊断。微小核糖核酸（microRNAs）是一类长度为18至25个核苷酸的单链非编码RNA，参与转录后调控过程。在人类医学领域，肿瘤样本中的miRNAs已被应用于肿瘤诊断、预后评估以及辅助靶向治疗，但在兽医医学中尚未得到广泛研究。本研究旨在通过RNA测序技术，分析犬脾脏血管肉瘤、犬脾脏结节性增生与正常犬脾脏之间的miRNAs差异表达情况。仅在脾脏血管肉瘤与结节性增生组之间，共鉴定出18个存在显著差异表达的miRNAs。其中倍数变化幅度最大的5个miRNAs分别为mir-193a、mir-450a、mir-503、mir-542及mir-876。另有4个miRNAs在脾脏血管肉瘤与结节性增生组、脾脏血管肉瘤与正常脾脏组中均存在显著差异表达，分别为mir-126、mir-150、mir-203及mir-452。本研究结果表明，犬脾脏血管肉瘤、结节性增生与正常脾脏的miRNA表达谱存在显著差异。由于多数脾脏肿物无法在术前实现明确诊断，本研究作为一项初步探索，其结果具备临床应用价值。犬脾脏肿物较为多发，因此有必要对本研究结果进行验证，以推动其作为临床诊断检测手段的潜在应用。实验整体设计：本研究共纳入15份样本进行miRNA表达分析，设置3个实验组，每组包含5个生物学重复。