Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma
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 medici...
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| Veröffentlicht in: | Genes 2024-08, Vol.15 (8), p.1024 |
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| creator | Hashimoto, Saki Hasan, M D Nazmul Arif, Mohammad Nozaki, Nobuhiro Husna, Al Asmaul Furusawa, Yu Sogawa, Takeshi Takahashi, Kaori Kuramoto, Tomohide Noguchi, Aki Takahashi, Masashi Yamato, Osamu Rahman, Md Mahfuzur Miura, Naoki |
| description | 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,
= 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950,
= 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. |
| doi_str_mv | 10.3390/genes15081024 |
| format | Article |
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= 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950,
= 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.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes15081024</identifier><identifier>PMID: 39202384</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adenoma ; Adenoma, Liver Cell - diagnosis ; Adenoma, Liver Cell - genetics ; Adenoma, Liver Cell - metabolism ; Adenoma, Liver Cell - pathology ; Adenoma, Liver Cell - veterinary ; Animals ; Bioinformatics ; Biomarkers ; Biomarkers, Tumor - genetics ; Blood & organ donations ; Breast cancer ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - veterinary ; Cell Line, Tumor ; Comparative analysis ; Diagnosis ; Diagnosis, Differential ; Diseases ; DNA repair ; Dog Diseases - diagnosis ; Dog Diseases - genetics ; Dogs ; Female ; Gene Expression Regulation, Neoplastic ; gene ontology ; Genes ; Genetic aspects ; genome ; Hepatocellular carcinoma ; Hepatocytes ; Hepatoma ; humans ; Identification and classification ; liver ; Liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Liver Neoplasms - veterinary ; Lymphatic system ; Mammary gland ; mammary glands ; medicine ; Melanoma ; Metastasis ; MicroRNAs ; mRNA ; mRNA processing ; neoplasm cells ; Physiological aspects ; Plasma ; prognosis ; proteasome endopeptidase complex ; Proteasomes ; Proteins ; Signal transduction ; Statistical analysis ; Transfer RNA ; tRNA Val ; Tumor cell lines ; Tumors ; Ubiquitin ; Variance analysis</subject><ispartof>Genes, 2024-08, Vol.15 (8), p.1024</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c402t-f3c3db194c6f8a574bfb23af6e09e79726d41f6f6c64064f4f56c2be46ed6b8b3</cites><orcidid>0000-0002-4625-5231 ; 0000-0003-3432-7696 ; 0000-0003-1965-9836 ; 0000-0002-8666-972X ; 0000-0002-4430-5645</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11353709/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11353709/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39202384$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hashimoto, Saki</creatorcontrib><creatorcontrib>Hasan, M D Nazmul</creatorcontrib><creatorcontrib>Arif, Mohammad</creatorcontrib><creatorcontrib>Nozaki, Nobuhiro</creatorcontrib><creatorcontrib>Husna, Al Asmaul</creatorcontrib><creatorcontrib>Furusawa, Yu</creatorcontrib><creatorcontrib>Sogawa, Takeshi</creatorcontrib><creatorcontrib>Takahashi, Kaori</creatorcontrib><creatorcontrib>Kuramoto, Tomohide</creatorcontrib><creatorcontrib>Noguchi, Aki</creatorcontrib><creatorcontrib>Takahashi, Masashi</creatorcontrib><creatorcontrib>Yamato, Osamu</creatorcontrib><creatorcontrib>Rahman, Md Mahfuzur</creatorcontrib><creatorcontrib>Miura, Naoki</creatorcontrib><title>Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma</title><title>Genes</title><addtitle>Genes (Basel)</addtitle><description>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,
= 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950,
= 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.</description><subject>Adenoma</subject><subject>Adenoma, Liver Cell - diagnosis</subject><subject>Adenoma, Liver Cell - genetics</subject><subject>Adenoma, Liver Cell - metabolism</subject><subject>Adenoma, Liver Cell - pathology</subject><subject>Adenoma, Liver Cell - veterinary</subject><subject>Animals</subject><subject>Bioinformatics</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Blood & organ donations</subject><subject>Breast cancer</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - veterinary</subject><subject>Cell Line, Tumor</subject><subject>Comparative analysis</subject><subject>Diagnosis</subject><subject>Diagnosis, Differential</subject><subject>Diseases</subject><subject>DNA repair</subject><subject>Dog Diseases - diagnosis</subject><subject>Dog Diseases - genetics</subject><subject>Dogs</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>gene ontology</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>genome</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatocytes</subject><subject>Hepatoma</subject><subject>humans</subject><subject>Identification and classification</subject><subject>liver</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - veterinary</subject><subject>Lymphatic system</subject><subject>Mammary gland</subject><subject>mammary glands</subject><subject>medicine</subject><subject>Melanoma</subject><subject>Metastasis</subject><subject>MicroRNAs</subject><subject>mRNA</subject><subject>mRNA processing</subject><subject>neoplasm cells</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>prognosis</subject><subject>proteasome endopeptidase complex</subject><subject>Proteasomes</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Statistical analysis</subject><subject>Transfer RNA</subject><subject>tRNA Val</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>Ubiquitin</subject><subject>Variance analysis</subject><issn>2073-4425</issn><issn>2073-4425</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkktv1TAQRiMEolXbJVsUiQ2bFL9ixysU3bYUqSoSAraW44xTV4l9sRNE-fU46oNeBKq98Hh85vPMaIriFUbHlEr0bgAPCdeowYiwZ8U-QYJWjJH6-SN7rzhK6RrlxRBBqH5Z7FFJEKEN2y9-tR3EqP083pSnP7cRUoK-nD9fttU3PZZnUQ8T-DmVG-3LE5dm54fFpav17jyU57DVczAwjsuoY_ZG43yYdGljmP4DtT2syGHxwuoxwdHdeVB8PTv9sjmvLj59-LhpLyqT850rSw3tOyyZ4bbRtWCd7QjVlgOSIKQgvGfYcssNZ4gzy2zNDemAceh513T0oHh_q7tdugl6k8uJelTb6CYdb1TQTu2-eHelhvBDYUxrKpDMCm_vFGL4vkCa1eTSWo72EJakKM6ckBLhp1EkpZCsFiv65i_0OizR51aslJD5eyL_UIMeQTlvQ87RrKKqbZBgWIpm1Tr-B5V3D5MzwYN12b8TUN0GmBhSimAf-oGRWmdL7cxW5l8_buIDfT9J9DdoJsqB</recordid><startdate>20240804</startdate><enddate>20240804</enddate><creator>Hashimoto, Saki</creator><creator>Hasan, M D Nazmul</creator><creator>Arif, Mohammad</creator><creator>Nozaki, Nobuhiro</creator><creator>Husna, Al Asmaul</creator><creator>Furusawa, Yu</creator><creator>Sogawa, Takeshi</creator><creator>Takahashi, Kaori</creator><creator>Kuramoto, Tomohide</creator><creator>Noguchi, Aki</creator><creator>Takahashi, Masashi</creator><creator>Yamato, Osamu</creator><creator>Rahman, Md Mahfuzur</creator><creator>Miura, Naoki</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4625-5231</orcidid><orcidid>https://orcid.org/0000-0003-3432-7696</orcidid><orcidid>https://orcid.org/0000-0003-1965-9836</orcidid><orcidid>https://orcid.org/0000-0002-8666-972X</orcidid><orcidid>https://orcid.org/0000-0002-4430-5645</orcidid></search><sort><creationdate>20240804</creationdate><title>Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma</title><author>Hashimoto, Saki ; Hasan, M D Nazmul ; Arif, Mohammad ; Nozaki, Nobuhiro ; Husna, Al Asmaul ; Furusawa, Yu ; Sogawa, Takeshi ; Takahashi, Kaori ; Kuramoto, Tomohide ; Noguchi, Aki ; Takahashi, Masashi ; Yamato, Osamu ; Rahman, Md Mahfuzur ; Miura, Naoki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-f3c3db194c6f8a574bfb23af6e09e79726d41f6f6c64064f4f56c2be46ed6b8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adenoma</topic><topic>Adenoma, Liver Cell - diagnosis</topic><topic>Adenoma, Liver Cell - genetics</topic><topic>Adenoma, Liver Cell - metabolism</topic><topic>Adenoma, Liver Cell - pathology</topic><topic>Adenoma, Liver Cell - veterinary</topic><topic>Animals</topic><topic>Bioinformatics</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Blood & organ donations</topic><topic>Breast cancer</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - veterinary</topic><topic>Cell Line, Tumor</topic><topic>Comparative analysis</topic><topic>Diagnosis</topic><topic>Diagnosis, Differential</topic><topic>Diseases</topic><topic>DNA repair</topic><topic>Dog Diseases - diagnosis</topic><topic>Dog Diseases - genetics</topic><topic>Dogs</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>gene ontology</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>genome</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatocytes</topic><topic>Hepatoma</topic><topic>humans</topic><topic>Identification and classification</topic><topic>liver</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - 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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,
= 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950,
= 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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39202384</pmid><doi>10.3390/genes15081024</doi><orcidid>https://orcid.org/0000-0002-4625-5231</orcidid><orcidid>https://orcid.org/0000-0003-3432-7696</orcidid><orcidid>https://orcid.org/0000-0003-1965-9836</orcidid><orcidid>https://orcid.org/0000-0002-8666-972X</orcidid><orcidid>https://orcid.org/0000-0002-4430-5645</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Genes, 2024-08, Vol.15 (8), p.1024 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Adenoma Adenoma, Liver Cell - diagnosis Adenoma, Liver Cell - genetics Adenoma, Liver Cell - metabolism Adenoma, Liver Cell - pathology Adenoma, Liver Cell - veterinary Animals Bioinformatics Biomarkers Biomarkers, Tumor - genetics Blood & organ donations Breast cancer Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - veterinary Cell Line, Tumor Comparative analysis Diagnosis Diagnosis, Differential Diseases DNA repair Dog Diseases - diagnosis Dog Diseases - genetics Dogs Female Gene Expression Regulation, Neoplastic gene ontology Genes Genetic aspects genome Hepatocellular carcinoma Hepatocytes Hepatoma humans Identification and classification liver Liver cancer Liver Neoplasms - genetics Liver Neoplasms - pathology Liver Neoplasms - veterinary Lymphatic system Mammary gland mammary glands medicine Melanoma Metastasis MicroRNAs mRNA mRNA processing neoplasm cells Physiological aspects Plasma prognosis proteasome endopeptidase complex Proteasomes Proteins Signal transduction Statistical analysis Transfer RNA tRNA Val Tumor cell lines Tumors Ubiquitin Variance analysis |
| title | Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma |
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