New Insights into the Impact of Human Papillomavirus on Oral Cancer in Young Patients: Proteomic Approach Reveals a Novel Role for S100A8

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Miranda-Galvis, Marisol ; Soares, Carolina Carneiro ; Carnielli, Carolina Moretto ; Buttura, Jaqueline Ramalho ; de Sa, Raisa Sales ; Kaminagakura, Estela ; Marchi, Fabio Albuquerque ; Leme, Adriana Franco Paes ; Pinto, Clovis A. Lopes ; Santos-Silva, Alan Roger ; Castilho, Rogerio Moraes ; Kowalski, Luiz Paulo ; Squarize, Cristiane Helena

• Tipo de documento: Artigo Científico
• Fonte: CELLS; v. 12, n. 9, p. 20-pg., 2023-05-05.

Resumo

Human papillomavirus (HPV) infection has recently been linked to a subset of cancers affecting the oral cavity. However, the molecular mechanisms underlying HPV-driven oral squamous cell carcinoma (OSCC) onset and progression are poorly understood. Methods: We performed MS-based proteomics profiling based on HPV status in OSCC in young patients, following biological characterization and cell assays to explore the proteome functional landscape. Results: Thirty-nine proteins are differentially abundant between HPV (+) and HPV (-) OSCC. Among them, COPS3, DYHC1, and S100A8 are unfavorable for tumor recurrence and survival, in contrast to A2M and Serpine1, low levels of which show an association with better DFS. Remarkably, S100A8 is considered an independent prognostic factor for lower survival rates, and at high levels, it alters tumor-associated immune profiling, showing a lower proportion of M1 macrophages and dendritic cells. HPV (+) OSCC also displayed the pathogen-associated patterns receptor that, when activated, triggered the S100A8 and NF?B inflammatory responses. Conclusion: HPV (+) OSCC has a peculiar microenvironment pattern distinctive from HPV (-), involving the expression of pathogen-associated pattern receptors, S100A8 overexpression, and NF?B activation and responses, which has important consequences in prognosis and may guide therapeutic decisions. (AU)

• Processo FAPESP: 16/03248-1 - Análise proteômica por espectrometria de massas do carcinoma de células escamosas oral em pacientes jovens
• Beneficiário: Marisol Miranda Galvis
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/16347-0 - Análise funcional de proteínas relacionadas ao hpv no carcinoma de células escamosas oral
• Beneficiário: Marisol Miranda Galvis
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado