HPV na cavidade oral

: abordagem de interatómica

Abstract

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.

Date of Award	22 Jul 2021
Original language	Portuguese
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Nuno Rosa (Supervisor), Maria José Correia (Co-Supervisor) & Ana Cristina Esteves (Co-Supervisor)