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Authors
Advisor(s)
Abstract(s)
O cancro colorretal (CCR) é o terceiro tipo de cancro mais comum no mundo e a quarta principal causa de morte associada ao cancro. A guanilato ciclase 2C (GUCY2C) é uma proteína transmembranar seletivamente expressa nas células epiteliais intestinais, tendo sido descrita em diversos estudos como um marcador em CCR. O objetivo do trabalho é estudar a GUCY2C e as respetivas vias de sinalização em doentes com CCR metastático em bases de dados públicas. Foi realizada uma pesquisa na base de dados pública cBioportal, sendo selecionada informação curada e anónima de 209 doentes com CCR. A informação sobre gânglios era escassa não sendo possível realizar análise, tendo-se efetuado apenas o estudo genético. Os resultados revelaram uma associação entre o estádio e mutações de KRAS (p=0,011) com mais mutações nos estádios mais elevados, ao contrário de BRAF onde não se encontrou associação (p=0,626). Verificou-se que mutações de perda de função da GUCY2C estão mais relacionadas aos estádios iniciais do cancro colorretal (p=3,735x10-13), o que aponta que a mutação de GUCY2C pode proteger da progressão do CRC. A mesma relação se verificou com as mutações de AKT (p=0,026) mas não com PTEN. Nenhuma associação foi encontrada entre as mutações de GUCY2C e as restantes mutações estudadas. Concluiu-se que há uma relação entre as mutações de GUCY2C e os estádios I e II em CCR, o que pode apontar à importância de GUCY2C como um biomarcador de prognóstico, e levar ao estudo de uma terapêutica de bloqueio que possa melhorar a sobrevida dos doentes. É necessária mais investigação para verificar estas associações do ponto de vista experimental.
ABSTRACT - Colorectal cancer (CRC) is the third most common type of cancer in the world and the fourth leading cause of cancer-related death. Guanylate cyclase 2C (GUCY2C) is a transmembrane protein selectively expressed in intestinal epithelial cells and has been described in several studies as a marker in CRC. This work aimed to study GUCY2C and its signaling pathways in patients with metastatic CRC in public databases. A search was carried out on the public database cBioportal, selecting curated and anonymized information from 209 patients with CRC. Information on lymph nodes was scarce and could not be analyzed; only the genetic study was carried out. The results revealed an association between stage and KRAS mutations (p=0.011) with more mutations in the higher stages, unlike BRAF where no association was found (p=0.626). GUCY2C loss-of-function mutations were found to be more related to the early stages of colorectal cancer (p=3.735x10-13), indicating that GUCY2C mutation may protect against CRC progression. The same relationship was found with AKT mutations (p=0.026) but not with PTEN. No association was found between GUCY2C mutations and the other mutations studied. It was concluded that there is a relationship between GUCY2C mutations and stages I and II in CRC, which could point to the importance of GUCY2C as a prognostic biomarker, and lead to the study of a blocking therapy that could improve patient survival. More research is needed to verify these associations from an experimental point of view.
ABSTRACT - Colorectal cancer (CRC) is the third most common type of cancer in the world and the fourth leading cause of cancer-related death. Guanylate cyclase 2C (GUCY2C) is a transmembrane protein selectively expressed in intestinal epithelial cells and has been described in several studies as a marker in CRC. This work aimed to study GUCY2C and its signaling pathways in patients with metastatic CRC in public databases. A search was carried out on the public database cBioportal, selecting curated and anonymized information from 209 patients with CRC. Information on lymph nodes was scarce and could not be analyzed; only the genetic study was carried out. The results revealed an association between stage and KRAS mutations (p=0.011) with more mutations in the higher stages, unlike BRAF where no association was found (p=0.626). GUCY2C loss-of-function mutations were found to be more related to the early stages of colorectal cancer (p=3.735x10-13), indicating that GUCY2C mutation may protect against CRC progression. The same relationship was found with AKT mutations (p=0.026) but not with PTEN. No association was found between GUCY2C mutations and the other mutations studied. It was concluded that there is a relationship between GUCY2C mutations and stages I and II in CRC, which could point to the importance of GUCY2C as a prognostic biomarker, and lead to the study of a blocking therapy that could improve patient survival. More research is needed to verify these associations from an experimental point of view.
Description
Mestrado em Tecnologias Clínico-Laboratoriais
Keywords
Cancro colorretal GUCY2C Mutação Metástases Colorectal cancer Mutation Metastases
Citation
Melo AV. GUCY2C como biomarcador de metástases ocultas em nódulos linfáticos de pacientes com cancro colorretal [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2024.
Publisher
Instituto Politécnico de Lisboa, Escola Superior de Tecnologia da Saúde de Lisboa