Análise da expressão de miR-21-5p e miR-105-5p no soro de pacientes com câncer gástrico
Data
2022-09-12
Autores
Santos, Yeda Beatriz Louredo dos 
Orientadores
Santos, Fernanda Wisnieski Caires dos
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O câncer gástrico (CG) é uma das mais frequentes e letais neoplasias do mundo.
Contudo, ainda existem poucas ferramentas eficazes para seu diagnóstico,
monitoramento e resposta ao tratamento. Estudos sobre biomarcadores são a grande
aposta da medicina personalizada nos últimos tempos, principalmente, em materiais
biológicos de fácil obtenção como a punção venosa periférica. A maioria dos estudos
da literatura em CG busca a identificação de biomarcadores em grupos étnicos
restritos. Previamente, nosso grupo de pesquisa identificou miR-21 e miR-105 como
alvos modulados epigeneticamente em modelos celulares e tecido gástrico neoplásico
provenientes de indivíduos da população brasileira. Objetivo: Avaliar se esses
miRNAs podem constituir potenciais biomarcadores minimamente invasivos de
diagnóstico, prognóstico e de monitoramento do CG. Métodos: A expressão de miR-
21-5p e miR-105-5p foi avaliada em amostras de soro de 50 participantes com CG e
de 14 participantes sem câncer e sem infecção por H. pylori. Os níveis desses miRNAs
foram monitorados após o tratamento cirúrgico em 21 participantes com CG de 3 a 48
meses. Os miRNAs foram quantificados por RT-qPCR e normalizados pela
combinação dos miRNAs de referência, miR-101-3p + miR-140-3p. Os dados de
expressão foram associados às variáveis clínicas e patológicas. Resultados: O miR-
21-5p apresentou expressão aumentada nos pacientes com CG em relação aos
participantes sem câncer (P < 0,01). Além disso, a expressão de miR-21-5p foi capaz
de discriminar esses indivíduos com acurácia de 84% (AUC = 0,88; P < 0,01). Após a
ressecção cirúrgica, não foram observadas alterações significativas na expressão de
miR-21-5p. A expressão de miR-105-5p nos participantes com CG não se diferenciou
dos controles, porém se alterou pós-cirurgicamente, com redução e aumento máximos
de 90% e 64%, respectivamente, de acordo com o tempo de monitoramento do
paciente. A expressão de miR-21-5p e miR-105-5p nas amostras pré e pós-cirúrgicas
não teve associação às características clínicas e patológicas. Conclusões: O miR-
21-5p e miR-105-5p demonstraram ser potenciais biomarcadores minimamente
invasivos para o diagnóstico do CG e de involução e sucesso do tratamento,
respectivamente.
Gastric cancer (GC) is one of the most frequent and lethal neoplasms in the world. However, there are still few effective tools for its diagnosis, monitoring and response to treatment. Studies on biomarkers are the major focus of personalized medicine in recent times, especially in easily obtainable biological materials such as peripheral venipuncture. Previously, our research group identified miR-21 and miR-105 as epigenetically modulated targets in GC cell lines and with dysregulated expression in neoplastic gastric tissue samples. Objective: To evaluate miR-21 and miR-105 may constitute potential minimally invasive biomarkers for gastric cancer diagnosis, prognosis, and monitoring. Methods: The expression of miR-21-5p and miR-105-5p was formed in cancer screening of 50 participants with GC and 14 participants without cancer and H. pylori infection. Additionally, the levels of these miRNAs were monitored after surgical treatment in 21 participants with GC from 3 to 48 months. The miRNAs were quantified by RT-qPCR and normalized by the combination of the reference miRNAs, miR-101-3p + miR-140-3p. Expression data were associated with clinical and pathological variables. Results: miR-21-5p showed increased expression in patients with GC compared to participants without cancer (P < 0.01). Furthermore, miR-21-5p expression was able to discriminate these individuals with an accuracy of 84% (AUC = 0,88; P < 0,01). After surgical resections, no significant changes in miR-21-5p expression were observed. The expression of miR-105-5p in participants with GC did not differ from controls, but changed post-surgically, with a reduction and maximum increase of 90% and 64%, respectively, according to the patient's monitoring time. The expression of miR-21-5p and miR-105-5p in pre- and post-surgical samples was not associated with clinical and pathological characteristics. Conclusions: miR-21-5p and miR-105-5p have been shown to be potential minimally invasive biomarkers for GC diagnosis and monitoring of these patients, respectively.
Gastric cancer (GC) is one of the most frequent and lethal neoplasms in the world. However, there are still few effective tools for its diagnosis, monitoring and response to treatment. Studies on biomarkers are the major focus of personalized medicine in recent times, especially in easily obtainable biological materials such as peripheral venipuncture. Previously, our research group identified miR-21 and miR-105 as epigenetically modulated targets in GC cell lines and with dysregulated expression in neoplastic gastric tissue samples. Objective: To evaluate miR-21 and miR-105 may constitute potential minimally invasive biomarkers for gastric cancer diagnosis, prognosis, and monitoring. Methods: The expression of miR-21-5p and miR-105-5p was formed in cancer screening of 50 participants with GC and 14 participants without cancer and H. pylori infection. Additionally, the levels of these miRNAs were monitored after surgical treatment in 21 participants with GC from 3 to 48 months. The miRNAs were quantified by RT-qPCR and normalized by the combination of the reference miRNAs, miR-101-3p + miR-140-3p. Expression data were associated with clinical and pathological variables. Results: miR-21-5p showed increased expression in patients with GC compared to participants without cancer (P < 0.01). Furthermore, miR-21-5p expression was able to discriminate these individuals with an accuracy of 84% (AUC = 0,88; P < 0,01). After surgical resections, no significant changes in miR-21-5p expression were observed. The expression of miR-105-5p in participants with GC did not differ from controls, but changed post-surgically, with a reduction and maximum increase of 90% and 64%, respectively, according to the patient's monitoring time. The expression of miR-21-5p and miR-105-5p in pre- and post-surgical samples was not associated with clinical and pathological characteristics. Conclusions: miR-21-5p and miR-105-5p have been shown to be potential minimally invasive biomarkers for GC diagnosis and monitoring of these patients, respectively.
Descrição
Citação
SANTOS, Yeda Beatriz Louredo dos. Análise da expressão de miR-21-5p e miR-105-5p no soro de pacientes com câncer gástrico. 2022. 116 f. Dissertação (Mestrado em Gastroenterologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2022.