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.