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Neves, Leandro Xavier
[1]
;
Granato, Daniela C.
[1]
;
Busso-Lopes, Ariane Fidelis
[1]
;
Carnielli, Carolina M.
[1]
;
de Sa Patroni, Fabio M.
[2]
;
De Rossi, Tatiane
[1]
;
Oliveira, Ana Karina
[1]
;
Ribeiro, Ana Carolina P.
[3]
;
Brandao, Thais Bianca
[3]
;
Rodrigues, Andre Nimtz
[4]
;
Lacerda, Pammela Araujo
[5]
;
Uno, Miyuki
[6]
;
Cervigne, Nilva K.
[5]
;
Santos-Silva, Alan Roger
[7]
;
Kowalski, Luiz Paulo
[8]
;
Lopes, Marcio Ajudarte
[7]
;
Paes Leme, Adriana F.
[1, 9]
Número total de Autores: 17
|
| Afiliação do(s) autor(es): | [1] Natl Ctr Res Energy & Mat, Brazilian Biosci Natl Lab, Campinas, SP - Brazil
[2] Univ Estadual Campinas, Mol Biol & Genet Engn Ctr, Campinas, SP - Brazil
[3] Sao Paulo Canc Inst, Dent Oncol Serv, Sao Paulo - Brazil
[4] Fac Med Jundiai, Dept Head & Neck Surg, Jundiai - Brazil
[5] Fac Med Jundiai, Dept Internal Med, Mol Biol & Cell Culture Lab, Jundiai - Brazil
[6] Sao Paulo Canc Inst, Ctr Translat Res Oncol, Sao Paulo - Brazil
[7] Univ Estadual Campinas, Piracicaba Dent Sch, Oral Diag Dept, Piracicaba, SP - Brazil
[8] Univ Sao Paulo, Fac Med, Head & Neck Surg, Sao Paulo - Brazil
[9] Ctr Nacl Pesquisa Energia & Mat, LNBio, Lab Nacl Biociencias, Rua Giuseppe Maximo Scolfaro, Campinas, SP - Brazil
Número total de Afiliações: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | MOLECULAR & CELLULAR PROTEOMICS; v. 20, 2021. |
| Citações Web of Science: | 0 |
| Resumo | |
Protease activity has been associated with pathological processes that can lead to cancer development and progression. However, understanding the pathological unbalance in proteolysis is challenging because changes can occur simultaneously at protease, their inhibitor, and substrate levels. Here, we present a pipeline that combines peptidomics, proteomics, and peptidase predictions for studying proteolytic events in the saliva of 79 patients and their association with oral squamous cell carcinoma (OSCC) prognosis. Our findings revealed differences in the saliva peptidome of patients with (pN+) or without (pN0) lymph-node metastasis and delivered a panel of ten endogenous peptides correlated with poor prognostic factors plus five molecules able to classify pN0 and pN+ patients (area under the receiver operating characteristic curve > 0.85). In addition, endopeptidases and exopeptidases putatively implicated in the processing of differential peptides were investigated using cancer tissue gene expression data from public repositories, reinforcing their association with poorer survival rates and prognosis in oral cancer. The dynamics of the OSCC-related proteolysis were further explored via the proteomic profiling of saliva. This revealed that peptidase/endopeptidase inhibitors exhibited reduced levels in the saliva of pN+ patients, as confirmed by selected reaction monitoring-mass spectrometry, while minor changes were detected in the level of saliva proteases. Taken together, our results indicated that proteolytic activity is accentuated in the saliva of patients with OSCC and lymph-node metastasis and, at least in part, is modulated by reduced levels of salivary peptidase inhibitors. Therefore, this integrated pipeline provided better comprehension and discovery of molecular features with implications in the oral cancer metastasis prognosis. (AU) | |
| Processo FAPESP: | 09/54067-3 - EMU: aquisição de um espectrômetro de massas acoplado a cromatografia líquida para permitir ampliar a capacidade de atendimento de usuários e disponibilizar novas tecnologias no Laboratório de Espectrometria de Massas do Centro de Biologia Molecular Estrutural (ABTLUS) |
| Beneficiário: | Adriana Franco Paes Leme |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |
| Processo FAPESP: | 18/11958-4 - Análise Proteômica de Vesículas Extracelulares Isoladas de Saliva e Plasma de Pacientes com Carcinoma de Células Escamosas para Estudo de Modificações Pós-Traducionais e Proposição de Marcadores Clínicos |
| Beneficiário: | Leandro Xavier Neves |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 18/18496-6 - O papel do álcool na transformação de células orais mediada por vesículas extracelulares |
| Beneficiário: | Adriana Franco Paes Leme |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 10/19278-0 - Estudo da regulação de ADAMs em câncer oral |
| Beneficiário: | Adriana Franco Paes Leme |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 16/07846-0 - Análise peptidômica de vesículas extracelulares originadas de linhagens celulares, saliva e plasma de pacientes com carcinoma de células escamosas da cavidade oral |
| Beneficiário: | Adriana Franco Paes Leme |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |