Preprint Article Version 1 This version is not peer-reviewed

Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma

Saki Hashimoto
,
MD Nazmul Hasan
* ,
Mohammad Arif
,
Nobuhiro Nozaki
,
Al Asmaul Husna
,
Yu Furusawa
,
Takeshi Sogawa
,
Kaori Takahashi
,
Tomohide Kuramoto
,
Aki Noguchi
,
Masashi Takahashi
,
Osamu Yamato
,
Md Mahfuzur Rahman
,
Naoki Miura
*
Version 1 : Received: 11 July 2024 / Approved: 11 July 2024 / Online: 11 July 2024 (16:36:26 CEST)

How to cite: Hashimoto, S.; Hasan, M. N.; Arif, M.; Nozaki, N.; Husna, A. A.; Furusawa, Y.; Sogawa, T.; Takahashi, K.; Kuramoto, T.; Noguchi, A.; Takahashi, M.; Yamato, O.; Rahman, M. M.; Miura, N. Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma. Preprints 2024, 2024070990. https://doi.org/10.20944/preprints202407.0990.v1 Hashimoto, S.; Hasan, M. N.; Arif, M.; Nozaki, N.; Husna, A. A.; Furusawa, Y.; Sogawa, T.; Takahashi, K.; Kuramoto, T.; Noguchi, A.; Takahashi, M.; Yamato, O.; Rahman, M. M.; Miura, N. Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma. Preprints 2024, 2024070990. https://doi.org/10.20944/preprints202407.0990.v1

Abstract

Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) can be difficult to differentiate but must be diagnosed correctly as treatment and prognosis for these tumors differ markedly. Relevant diagnostic biomarkers are thus needed, and those identified in dogs may have utility in human medicine because of the similarities between human and canine HCA and HCC. A tRNA-derived fragment (tRF), tRNA-Val, is a promising potential biomarker for canine mammary gland tumors but has not previously been investigated in hepatic tumors. Accordingly, we aimed to elucidate the potential utility of tRNA-Val as a biomarker for canine HCA and HCC using clinical samples (tumor tissue and plasma extracellular vesicles [EVs]) and tumor cell lines with qRT-PCR assays. We also investigated relevant functions and signaling pathways with bioinformatic analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes). tRNA-Val was markedly downregulated in HCC tumor tissue versus HCA tumor tissue and normal liver tissue, and a similar trend was shown in plasma EVs and HCC cell lines versus healthy controls. Based on areas under the receiver operating characteristic curves (AUCs), tRNA-Val significantly distinguished HCC (AUC=1.00, P=0.001) from healthy controls in plasma EVs and HCC from HCA (AUC=0.950, P=0.01). Bioinformatics analysis revealed that tRNA-Val may be primarily involved in DNA repair, mRNA processing, and splicing and may be linked to the N-glycan and ubiquitin-mediated proteasome pathways. This is the first report on the expression of tRNA-Val in canine HCC and HCA, and its possible functions and signaling pathways. We suggest that tRNA-Val could be a promising novel biomarker to distinguish canine HCC from HCA. This study provides evidence for a greater understanding of the role played by tRNA-Val in the development of canine HCC.

Keywords

tRNA-Val; canine hepatocellular carcinoma; canine hepatocellular adenoma

Subject

Biology and Life Sciences, Animal Science, Veterinary Science and Zoology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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