Salivary biomarkers in head and neck cancer

Detalhes bibliográficos
Autor(a) principal: Rentroia, Mara Ivone Santos
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/30290
Resumo: Head and neck cancer (HNC) are a group of cancers which occur in the organs from the anatomical area referred. The HNC staging system is generalized for most subtypes of HNC and restricted for the seven classifying stages of this cancer, which affects the diagnosis and, therefore, the treatment. The possible biomarkers identified for HNC are either non-specific or still waiting for clinical validations. Exosomes are nanovesicles which reflect the molecular composition of the cell of origin, including tumour cells, and can be found in biofluids as saliva, a proximal and easily accessible fluid for HNC. As exosome’ purification methods are being developed, the study of the proteome of salivary exosomes of HNC patients is a promising approach for identification of specific biomarkers for HNC and early diagnosis and prognosis of the cancer. In this thesis project, unstimulated saliva was collected from fifteen HNC patients and three healthy subjects and exosomes were extracted. Protein quantification was performed, and the proteins were analysed by LC-MS, after protein separation with SDS-PAGE and in-gel trypsin digestion. The proteomes of salivary exosomes of HNC demonstrated to be involved in a panoply of biological processes mainly focused in exocytosis, inflammatory response and tumour-related processes, which were expected in this study. The overexpression of α-amylase and immunoglobulin A in salivary exosomes of HNC, when compared with the healthy controls, is considered as a potential HNC biomarker. From the several proteins exclusively in either sample 1, 2, 8, 10, 14 and 15, suprabasin, protein S100-A7, S100-P and cathepsin B were already described as HNC possible biomarker in another type of samples. This study demonstrated that the salivary exosomes are capable to reflect the pathophysiological status of HNC. Furthermore, overexpression of α-amylase and immunoglobulin A in salivary exosomes may be a non-specific biomarker of HNC and the previously described HNC biomarkers need to be further studied in order to understand in which conditions they are expressed.
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spelling Salivary biomarkers in head and neck cancerHead and Neck CancerSalivaExosomeProteomeHead and neck cancer (HNC) are a group of cancers which occur in the organs from the anatomical area referred. The HNC staging system is generalized for most subtypes of HNC and restricted for the seven classifying stages of this cancer, which affects the diagnosis and, therefore, the treatment. The possible biomarkers identified for HNC are either non-specific or still waiting for clinical validations. Exosomes are nanovesicles which reflect the molecular composition of the cell of origin, including tumour cells, and can be found in biofluids as saliva, a proximal and easily accessible fluid for HNC. As exosome’ purification methods are being developed, the study of the proteome of salivary exosomes of HNC patients is a promising approach for identification of specific biomarkers for HNC and early diagnosis and prognosis of the cancer. In this thesis project, unstimulated saliva was collected from fifteen HNC patients and three healthy subjects and exosomes were extracted. Protein quantification was performed, and the proteins were analysed by LC-MS, after protein separation with SDS-PAGE and in-gel trypsin digestion. The proteomes of salivary exosomes of HNC demonstrated to be involved in a panoply of biological processes mainly focused in exocytosis, inflammatory response and tumour-related processes, which were expected in this study. The overexpression of α-amylase and immunoglobulin A in salivary exosomes of HNC, when compared with the healthy controls, is considered as a potential HNC biomarker. From the several proteins exclusively in either sample 1, 2, 8, 10, 14 and 15, suprabasin, protein S100-A7, S100-P and cathepsin B were already described as HNC possible biomarker in another type of samples. This study demonstrated that the salivary exosomes are capable to reflect the pathophysiological status of HNC. Furthermore, overexpression of α-amylase and immunoglobulin A in salivary exosomes may be a non-specific biomarker of HNC and the previously described HNC biomarkers need to be further studied in order to understand in which conditions they are expressed.O cancro da cabeça e pescoço (CCP) corresponde a um grupo de cancros que ocorrem nos órgãos da área anatómica referida. O sistema de classificação do CCP é generalizado para a maioria dos subtipos de CCP e restrito aos sete estágios de classificação desse cancro, o que afeta o diagnóstico e, portanto, o tratamento. Os possíveis biomarcadores identificados para CCP ou não são específicos, ou ainda aguardam validações clínicas. Os exossomas são nanovesículas que refletem a composição molecular da sua célula de origem, inclusive células tumorais, e podem ser encontrados em bio fluídos como saliva, um fluído proximal e de fácil acesso. À medida que os métodos de purificação dos exossomas estão a ser desenvolvidos, o estudo do proteoma de exossomas salivares de pacientes com CCP surge como uma abordagem promissora para a identificação de biomarcadores específicos para o mesmo, e diagnóstico e prognóstico precoces do cancro. Neste projeto de tese, a saliva não estimulada foi recolhida de quinze pacientes e três sujeitos saudáveis com CCP e os exossomas foram extraídos. A quantificação de proteínas foi realizada e as proteínas foram analisadas por LC-MS, após separação das proteínas com SDS-PAGE e digestão com tripsina em gel. Os proteomas dos exossomas salivares do HNC demonstraram estar envolvidos numa panóplia de processos biológicos direcionados principalmente para exocitose, resposta inflamatória e processos relacionados a tumores, algo esperado neste estudo. A sobre expressão de α-amilase e imunoglobulina A nos exossomas salivares de HNC, quando comparada com os controlos saudáveis, é considerada um potencial biomarcador de CCP. Das várias proteínas exclusivas nas amostras 1, 2, 8, 10, 14 e 15, a suprabasina, a proteína S100-A7, S100-P e a catepsina B já foram descritas como possíveis biomarcadores do HNC noutro tipo de amostras. Assim, este estudo demonstrou que os exossomas salivares são capazes de refletir o estatuto fisiopatológico do HNC e que a sobre expressão de α-amilase e imunoglobulina A em exossomas salivares pode ser um biomarcador não específico de HNC. Relativamente aos restantes biomarcadores de HNC descritos serão necessários mais estudos para entender em que condições são expressos.2022-01-03T00:00:00Z2019-12-19T00:00:00Z2019-12-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/30290engRentroia, Mara Ivone Santosinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:58:34Zoai:ria.ua.pt:10773/30290Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:02:26.393553Repositório 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 Salivary biomarkers in head and neck cancer
title Salivary biomarkers in head and neck cancer
spellingShingle Salivary biomarkers in head and neck cancer
Rentroia, Mara Ivone Santos
Head and Neck Cancer
Saliva
Exosome
Proteome
title_short Salivary biomarkers in head and neck cancer
title_full Salivary biomarkers in head and neck cancer
title_fullStr Salivary biomarkers in head and neck cancer
title_full_unstemmed Salivary biomarkers in head and neck cancer
title_sort Salivary biomarkers in head and neck cancer
author Rentroia, Mara Ivone Santos
author_facet Rentroia, Mara Ivone Santos
author_role author
dc.contributor.author.fl_str_mv Rentroia, Mara Ivone Santos
dc.subject.por.fl_str_mv Head and Neck Cancer
Saliva
Exosome
Proteome
topic Head and Neck Cancer
Saliva
Exosome
Proteome
description Head and neck cancer (HNC) are a group of cancers which occur in the organs from the anatomical area referred. The HNC staging system is generalized for most subtypes of HNC and restricted for the seven classifying stages of this cancer, which affects the diagnosis and, therefore, the treatment. The possible biomarkers identified for HNC are either non-specific or still waiting for clinical validations. Exosomes are nanovesicles which reflect the molecular composition of the cell of origin, including tumour cells, and can be found in biofluids as saliva, a proximal and easily accessible fluid for HNC. As exosome’ purification methods are being developed, the study of the proteome of salivary exosomes of HNC patients is a promising approach for identification of specific biomarkers for HNC and early diagnosis and prognosis of the cancer. In this thesis project, unstimulated saliva was collected from fifteen HNC patients and three healthy subjects and exosomes were extracted. Protein quantification was performed, and the proteins were analysed by LC-MS, after protein separation with SDS-PAGE and in-gel trypsin digestion. The proteomes of salivary exosomes of HNC demonstrated to be involved in a panoply of biological processes mainly focused in exocytosis, inflammatory response and tumour-related processes, which were expected in this study. The overexpression of α-amylase and immunoglobulin A in salivary exosomes of HNC, when compared with the healthy controls, is considered as a potential HNC biomarker. From the several proteins exclusively in either sample 1, 2, 8, 10, 14 and 15, suprabasin, protein S100-A7, S100-P and cathepsin B were already described as HNC possible biomarker in another type of samples. This study demonstrated that the salivary exosomes are capable to reflect the pathophysiological status of HNC. Furthermore, overexpression of α-amylase and immunoglobulin A in salivary exosomes may be a non-specific biomarker of HNC and the previously described HNC biomarkers need to be further studied in order to understand in which conditions they are expressed.
publishDate 2019
dc.date.none.fl_str_mv 2019-12-19T00:00:00Z
2019-12-19
2022-01-03T00:00:00Z
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