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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Peptidomics-Driven Strategy Reveals Peptides and Predicted Proteases Associated With Oral Cancer Prognosis

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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]
Total Authors: 17
[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
Total Affiliations: 9
Document type: Journal article
Web of Science Citations: 0

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)

FAPESP's process: 09/54067-3 - Acquisition of a mass spectrometer coupled to a liquid chromatography system for increasing the capacity to meet the needs of users and for making new technologies available in the Laboratory of Mass Spectrometry
Grantee:Adriana Franco Paes Leme
Support type: Multi-user Equipment Program
FAPESP's process: 18/11958-4 - Proteomic Analysis of Extracellular Vesicles from Saliva and Plasma of Patients with Squamous Cells Carcinoma and the Study of Post-Translational Modifications and Identification of Disease Markers
Grantee:Leandro Xavier Neves
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 18/18496-6 - The role of alcohol treated-extracellular vesicles in oral cells transformation
Grantee:Adriana Franco Paes Leme
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/19278-0 - Study of regulation of ADAMs in oral cancer
Grantee:Adriana Franco Paes Leme
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 16/07846-0 - Peptidomic analysis of extracelular vesicles originated from cell lines, saliva and plasma from oral squamous cell carcinoma
Grantee:Adriana Franco Paes Leme
Support type: Regular Research Grants