Novel Y RNA-Derived Fragments Can Differentiate Canine Hepatocellular Carcinoma from Hepatocellular Adenoma

Simple Summary Hepatocellular carcinoma (HCC) is difficult to distinguish from hepatocellular adenoma (HCA) in dogs, and HCC may develop from HCA, according to recent reports. Therefore, urgent research is needed to establish a reliable biomarker for the early detection of these hepatic diseases. Noncoding RNAs (ncRNAs) could be a very useful tool for diagnosing hepatic diseases. Y RNA is a regulatory RNA type with a sequence of 80-110 nucleotides. In this study, we investigated novel Y RNA-derived fragments, namely Y RNA, which we previously investigated in canine mammary gland tumors and found that they could differentiate between benign and malignant tumors. Accordingly, we decided to investigate Y RNA in canine HCC and HCA, which has not been attempted before in either humans or dogs. We report that Y RNA can discriminate canine HCC from HCA and could be a promising biomarker for diagnosing canine HCC and HCA.Abstract Hepatocellular carcinomas (HCC) are common tumors, whereas hepatocellular adenomas (HCA) are rare, benign tumors in dogs. The aberrant expression of noncoding RNAs (ncRNAs) plays a pivotal role in HCC tumorigenesis and progression. Among ncRNAs, micro RNAs have been widely researched in human HCC, but much less widely in canine HCC. However, Y RNA-derived fragments have yet to be investigated in canine HCC and HCA. This study targeted canine HCC and HCA patients. We used qRT-PCR to determine Y RNA expression in clinical tissues, plasma, and plasma extracellular vesicles, and two HCC cell lines (95-1044 and AZACH). Y RNA was significantly decreased in tissue, plasma, and plasma extracellular vesicles for canine HCC versus canine HCA and healthy controls. Y RNA was decreased in 95-1044 and AZACH cells versus normal liver tissue and in AZACH versus 95-1044 cells. In plasma samples, Y RNA levels were decreased in HCC versus HCA and Healthy controls and increased in HCA versus Healthy controls. Receiver operating characteristic analysis showed that Y RNA could be a promising biomarker for distinguishing HCC from HCA and healthy controls. Overall, the dysregulated expression of Y RNA can distinguish canine HCC from HCA. However, further research is necessary to elucidate the underlying Y RNA-related molecular mechanisms in hepatocellular neoplastic diseases. To the best of our knowledge, this is the first report on the relative expression of Y RNA in canine HCC and HCA.