TY - JOUR
T1 - New Insights into the Impact of Human Papillomavirus on Oral Cancer in Young Patients
T2 - Proteomic Approach Reveals a Novel Role for S100A8
AU - Miranda-Galvis, Marisol
AU - Carneiro Soares, Carolina
AU - Moretto Carnielli, Carolina
AU - Ramalho Buttura, Jaqueline
AU - Sales de Sá, Raisa
AU - Kaminagakura, Estela
AU - Marchi, Fabio Albuquerque
AU - Paes Leme, Adriana Franco
AU - Lópes Pinto, Clóvis A.
AU - Santos-Silva, Alan Roger
AU - Moraes Castilho, Rogerio
AU - Kowalski, Luiz Paulo
AU - Squarize, Cristiane Helena
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/5
Y1 - 2023/5
N2 - 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 NFκB inflammatory responses. Conclusion: HPV (+) OSCC has a peculiar microenvironment pattern distinctive from HPV (−), involving the expression of pathogen-associated pattern receptors, S100A8 overexpression, and NFκB activation and responses, which has important consequences in prognosis and may guide therapeutic decisions.
AB - 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 NFκB inflammatory responses. Conclusion: HPV (+) OSCC has a peculiar microenvironment pattern distinctive from HPV (−), involving the expression of pathogen-associated pattern receptors, S100A8 overexpression, and NFκB activation and responses, which has important consequences in prognosis and may guide therapeutic decisions.
KW - HPV
KW - S100A8
KW - oral cancer
KW - prognosis
KW - proteomics
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U2 - 10.3390/cells12091323
DO - 10.3390/cells12091323
M3 - Article
C2 - 37174723
AN - SCOPUS:85159220696
SN - 2073-4409
VL - 12
JO - Cells
JF - Cells
IS - 9
M1 - 1323
ER -