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Authors
Abstract(s)
Introdução: A infeção por vírus do papiloma humano (HPV) é a infeção transmissível
mais comum. Sabe-se que a infeção por HPV pode originar diferentes tipos de cancro
oral. Os mecanismos moleculares que explicam esta relação não estão ainda
esclarecidos.
Objetivos: Este trabalho visa estudar os mecanismos moleculares que se
estabelecem entre o HPV e o hospedeiro após infeção, e sua relação com cancro oral
incluindo a proposta de um painel de biomarcadores salivares caraterístico desta
relação.
Materiais e métodos: Foi anotada a informação do proteoma salivar relacionado com
a infeção por HPV para atualização da base de dados SalivaTecDB. Realizou-se uma
análise funcional para identificação de um potencial painel de biomarcadores salivares
caraterístico do cancro oral associado a infeção por HPV, usando as ferramentas
PANTHER, DAVID e STRING. A previsão das PPIs foi realizada com o algoritmo
OralInt. A análise funcional das PPIs foi realizada usando os programas Cytoscape®
e CluGO+CluePedia.
Resultados: Foram anotadas 514 proteínas. A análise funcional permitiu propor como
moléculas a integrar um painel de biomarcadores as proteínas RPRD2, PSCA, MCM2,
MCM5, CDKN2A, BAK1, HSPA1A, HSPA5, HSPA8, TANK, MAP2K1. O OralInt
permitiu prever um total de 18389 interações entre HPV e o hospedeiro, sendo que
dessas, 447 são PPIs de alta confiança (Score ≥0,75). A análise funcional da rede
permitiu identificar “Pathways” que poderão estar alterados após a infeção por HPV.
Nomeadamente: “Parkinson disease”, Lipid and atherosclerosis”, “DNA Replication”,
Proteasome”, Estrogen signaling pathway” sendo que estes últimos poderão
relacionar infeção por HPV com o cancro oral.
Conclusão: Este estudo permitiu propor um painel de 8 biomarcadores de cancro oral
em pacientes previamente infetados por HPV. A análise de interatómica permitiu
elucidar que a infeção por HPV pode alterar “Pathways” como “Estrogen signaling
pathway”, “Lipid and atherosclerosis”, “DNA Replication” e “Proteasome”,
potencialmente associados a cancro.
Introduction: Human papillomavirus (HPV) is the most common transmitted infection. It is known that HPV infection can lead to different types of oral cancer. However, the molecular interactions that explain this relationship are not yet clear. Objective: The purpose of this research is to study the molecular mechanisms that are established between the human papillomavirus (HPV) and the host in the oral infection context, and its relationship with the clinical manifestations of the infection, in order to design a panel of salivary biomarkers characteristic of the oral cancer associated with HPV infection. Materials and methods: Annotations of information regarding salivary proteome related to HPV infection were made to update the SalivaTecDB database. A functional analysis was done to identify a potential panel of salivary biomarkers characteristic of the oral cancer after HPV infection, the interaction network was done using the following tools PANTHER, DAVID, STRING. The prediction of PPIs was performed with the OralInt algorithm. Functional analysis of PPIs was performed using Cytoscape® and CluGO+CluePedia programs. Results: 514 different proteins were annotated. The functional analysis allowed us to propose as molecules to integrate a panel of biomarkers the proteins RPRD2, PSCA, MCM2, MCM5, CDKN2A, BAK1, HSPA1A, HSPA5, HSPA8, TANK, MAP2K1. OralInt allowed to predict a total of 18389 interactions between the HPV and the host, of which 447 are highly reliable PPIs (Score ≥0.75). The functional analysis of the network allowed the identification of “Pathways” that could be altered after the HPV infection. Namely: “Parkinson disease”, Lipid and atherosclerosis”, “DNA Replication”, Proteasome, Estrogen signaling pathway” and the latter may relate HPV infection with oral cancer. Conclusion: This study allowed us to propose 8 proteins (RPRD2, PSCA, MCM2, CDKN2A, BAK1, HSPA1A, TANK, MAP2K1), as biomarkers of oral cancer in patients previously infected with HPV. The interatomic analysis allowed to elucidate that HPV infection can alter “Pathways” such as “Estrogen signaling pathway”, Lipid and atherosclerosis”, “DNA Replication” and “Proteasome”, potentially associated with cancer.
Introduction: Human papillomavirus (HPV) is the most common transmitted infection. It is known that HPV infection can lead to different types of oral cancer. However, the molecular interactions that explain this relationship are not yet clear. Objective: The purpose of this research is to study the molecular mechanisms that are established between the human papillomavirus (HPV) and the host in the oral infection context, and its relationship with the clinical manifestations of the infection, in order to design a panel of salivary biomarkers characteristic of the oral cancer associated with HPV infection. Materials and methods: Annotations of information regarding salivary proteome related to HPV infection were made to update the SalivaTecDB database. A functional analysis was done to identify a potential panel of salivary biomarkers characteristic of the oral cancer after HPV infection, the interaction network was done using the following tools PANTHER, DAVID, STRING. The prediction of PPIs was performed with the OralInt algorithm. Functional analysis of PPIs was performed using Cytoscape® and CluGO+CluePedia programs. Results: 514 different proteins were annotated. The functional analysis allowed us to propose as molecules to integrate a panel of biomarkers the proteins RPRD2, PSCA, MCM2, MCM5, CDKN2A, BAK1, HSPA1A, HSPA5, HSPA8, TANK, MAP2K1. OralInt allowed to predict a total of 18389 interactions between the HPV and the host, of which 447 are highly reliable PPIs (Score ≥0.75). The functional analysis of the network allowed the identification of “Pathways” that could be altered after the HPV infection. Namely: “Parkinson disease”, Lipid and atherosclerosis”, “DNA Replication”, Proteasome, Estrogen signaling pathway” and the latter may relate HPV infection with oral cancer. Conclusion: This study allowed us to propose 8 proteins (RPRD2, PSCA, MCM2, CDKN2A, BAK1, HSPA1A, TANK, MAP2K1), as biomarkers of oral cancer in patients previously infected with HPV. The interatomic analysis allowed to elucidate that HPV infection can alter “Pathways” such as “Estrogen signaling pathway”, Lipid and atherosclerosis”, “DNA Replication” and “Proteasome”, potentially associated with cancer.
Description
Keywords
Proteínas salivares Proteómica Biomarcadores HPV Interatómica Salivary proteins Proteomics Biomarkers Interatomic