Proteína desacopladora 2 e o Transdutor e Ativador de Transcrição 1 são alvos das oncoproteínas do Papilomavírus Humano e podem ser marcadores prognósticos para o desenvolvimento do cancro do colo do útero.

• Processo: 25/24836-8
• Modalidade de apoio: Auxílio à Pesquisa - Publicações científicas - Artigo
• Data de Início da vigência: 01 de março de 2026
• Data de Término da vigência: 31 de agosto de 2026
• Área do conhecimento: Ciências da Saúde - Medicina
• Pesquisador responsável: Ana Paula Lepique
• Beneficiário: Ana Paula Lepique
• Instituição Sede: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brasil
• Município da Instituição Sede: São Paulo
• Assunto(s): Biomarcadores Neoplasias do colo uterino Infecções por Papillomavirus
• Palavra(s)-Chave do Pesquisador: biomarcadores | câncer cervical | papilomavírus humano | Stat1 | Ucp2 | Câncer ginecológico

Resumo

Cervical cancer, almost always caused by persistent high-risk Human Papillomavirus infection, remains a major public health concern in developing countries. Prognostic markers that aid in managing patients with precursor lesions could enhance healthcare. We compared gene expression between low- and high-grade cervical intraepithelial lesions, focusing on inflammation- and oxidative stress-related genes. Among the differentially expressed genes, we identified STAT1 (Signal Transducer and Activator of Transcription 1) and UCP2 (Uncoupling Protein 2), which we chose for validation because of their known roles in other cancer types. Using immunodetection in monolayer and organotypic cultures, we examined whether HPV oncoproteins could regulate these proteins' expression. We then evaluated their expression through immunohistochemistry in two groups: one with patients having precursor lesions and cancer, and another with only cervical cancer patients. In culture, HaCaT cells transduced with E6/E7 HPV oncogenes altered the expression of both proteins, mainly in organotypic cultures. In patients, UCP2 and STAT1 levels increased with the grade of cervical precursor lesions, and a strong correlation between their expressions was observed. Although very few cancer samples showed nuclear STAT1 expression, an indication of protein activation, these were linked to poor prognosis. Conversely, positive UCP2 expression was associated with better survival and lower recurrence. Our results indicate that HPV oncoproteins influence UCP2 and STAT1 expression, and these proteins could serve as prognostic markers for patients with precursor lesions and, in the case of UCP2, cervical cancer. (AU)