The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/150342 |
Resumo: | Cytosine modifications at the 5-carbon position play an important role in the regulation of gene expression, and its deregulation is considered a hallmark of cancer. Recent studies demonstrate that 5-hydroxymethylcytosine (5-hmC) generated through 5-methylcytosine (5-mC) oxidation is significantly depleted in several human cancers. Although its role in tumour progression is still unknown, the 5-hmC loss has been proposed as a marker of tumour malignancy. Concerning thyroid tumours, the literature is scarce, and the studies are sparse in a number of cases and diversity of histotypes, not allowing clear conclusions. In this work, we evaluated the levels of 5-hmC, by immunohistochemistry, in a retrospective series of 318 thyroid tumours, including benign, low-risk, and malignant tumours, classified according to the 4th edition of WHO, and correlated its expression with demographic and clinicopathological features of the patients and tumours, aiming to verify whether 5-hmC levels can be used as a diagnostic, prognostic or therapeutic marker. Our data show a significant association between loss of expression of 5-hmC and extrathyroidal extension, invasive/infiltrative capsule status, lymphovascular invasion, bilaterality, multifocality, tumour malignancy, and an unprecedented link with oncocytic morphology. Additionally, in a subgroup of 183 papillary thyroid carcinoma (PTC) cases, we also observed a statistically significant loss of 5-hmC in cases with TERT promoter mutations and distant metastasis. Our study evidences an important role for 5-hmC in thyroid tumourigenesis and indicates that 5-hmC levels have the potential to be used as a diagnostic and prognostic marker, however, more studies are needed to fully verify its potential. |
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The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasmCiências da saúdeHealth sciencesCytosine modifications at the 5-carbon position play an important role in the regulation of gene expression, and its deregulation is considered a hallmark of cancer. Recent studies demonstrate that 5-hydroxymethylcytosine (5-hmC) generated through 5-methylcytosine (5-mC) oxidation is significantly depleted in several human cancers. Although its role in tumour progression is still unknown, the 5-hmC loss has been proposed as a marker of tumour malignancy. Concerning thyroid tumours, the literature is scarce, and the studies are sparse in a number of cases and diversity of histotypes, not allowing clear conclusions. In this work, we evaluated the levels of 5-hmC, by immunohistochemistry, in a retrospective series of 318 thyroid tumours, including benign, low-risk, and malignant tumours, classified according to the 4th edition of WHO, and correlated its expression with demographic and clinicopathological features of the patients and tumours, aiming to verify whether 5-hmC levels can be used as a diagnostic, prognostic or therapeutic marker. Our data show a significant association between loss of expression of 5-hmC and extrathyroidal extension, invasive/infiltrative capsule status, lymphovascular invasion, bilaterality, multifocality, tumour malignancy, and an unprecedented link with oncocytic morphology. Additionally, in a subgroup of 183 papillary thyroid carcinoma (PTC) cases, we also observed a statistically significant loss of 5-hmC in cases with TERT promoter mutations and distant metastasis. Our study evidences an important role for 5-hmC in thyroid tumourigenesis and indicates that 5-hmC levels have the potential to be used as a diagnostic and prognostic marker, however, more studies are needed to fully verify its potential.2023-05-242023-05-24T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://hdl.handle.net/10216/150342TID:203521803porJoão Pedro Cerveira Gonçalvesinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-16T01:25:00Zoai:repositorio-aberto.up.pt:10216/150342Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:39:37.647141Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm |
title |
The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm |
spellingShingle |
The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm João Pedro Cerveira Gonçalves Ciências da saúde Health sciences |
title_short |
The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm |
title_full |
The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm |
title_fullStr |
The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm |
title_full_unstemmed |
The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm |
title_sort |
The role of 5-hydroxymethylcytosine as a potential epigenetic biomarker in a large series of thyroid neoplasm |
author |
João Pedro Cerveira Gonçalves |
author_facet |
João Pedro Cerveira Gonçalves |
author_role |
author |
dc.contributor.author.fl_str_mv |
João Pedro Cerveira Gonçalves |
dc.subject.por.fl_str_mv |
Ciências da saúde Health sciences |
topic |
Ciências da saúde Health sciences |
description |
Cytosine modifications at the 5-carbon position play an important role in the regulation of gene expression, and its deregulation is considered a hallmark of cancer. Recent studies demonstrate that 5-hydroxymethylcytosine (5-hmC) generated through 5-methylcytosine (5-mC) oxidation is significantly depleted in several human cancers. Although its role in tumour progression is still unknown, the 5-hmC loss has been proposed as a marker of tumour malignancy. Concerning thyroid tumours, the literature is scarce, and the studies are sparse in a number of cases and diversity of histotypes, not allowing clear conclusions. In this work, we evaluated the levels of 5-hmC, by immunohistochemistry, in a retrospective series of 318 thyroid tumours, including benign, low-risk, and malignant tumours, classified according to the 4th edition of WHO, and correlated its expression with demographic and clinicopathological features of the patients and tumours, aiming to verify whether 5-hmC levels can be used as a diagnostic, prognostic or therapeutic marker. Our data show a significant association between loss of expression of 5-hmC and extrathyroidal extension, invasive/infiltrative capsule status, lymphovascular invasion, bilaterality, multifocality, tumour malignancy, and an unprecedented link with oncocytic morphology. Additionally, in a subgroup of 183 papillary thyroid carcinoma (PTC) cases, we also observed a statistically significant loss of 5-hmC in cases with TERT promoter mutations and distant metastasis. Our study evidences an important role for 5-hmC in thyroid tumourigenesis and indicates that 5-hmC levels have the potential to be used as a diagnostic and prognostic marker, however, more studies are needed to fully verify its potential. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-05-24 2023-05-24T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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https://hdl.handle.net/10216/150342 TID:203521803 |
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https://hdl.handle.net/10216/150342 |
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TID:203521803 |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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