Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer

2018; Nature Portfolio; Volume: 9; Issue: 1 Linguagem: Inglês

10.1038/s41467-018-05696-2

2041-1723

Carolina Moretto Carnielli, Carolina Carneiro Soares Macedo, Tatiane De Rossi, Daniela Campos Granato, César Rivera, Romênia R. Domingues, Bianca Alves Pauletti, Sami Yokoo, Henry Heberle, Ariane F. Busso‐Lopes, Nilva K. Cervigne, Íris Sawazaki‐Calone, Gabriela Vaz Meirelles, Fábio Albuquerque Marchi, Guilherme P. Telles, Rosane Minghim, Ana Carolina Prado Ribeiro, Thaís Bianca Brandão, Gilberto de Castro, Wilfredo Alejandro González‐Arriagada, Alexandre F. Gomes, Fabio Penteado, Alan Roger Santos‐Silva, Márcio Ajudarte Lopes, Priscila Campioni Rodrigues, Elias Sundquist, Tuula Salo, Sabrina Daniela da Silva, Moulay A. Alaoui‐Jamali, Edgard Graner, Jay W. Fox, Ricardo Della Coletta, Adriana Franco Paes Leme,

Peptidase Inhibition and Analysis

Abstract Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological and molecular characteristics limiting the standard tumor−node−metastasis prognosis classification. Therefore, defining biological signatures that allow assessing the prognostic outcomes for OSCC patients would be of great clinical significance. Using histopathology-guided discovery proteomics, we analyze neoplastic islands and stroma from the invasive tumor front (ITF) and inner tumor to identify differentially expressed proteins. Potential signature proteins are prioritized and further investigated by immunohistochemistry (IHC) and targeted proteomics. IHC indicates low expression of cystatin-B in neoplastic islands from the ITF as an independent marker for local recurrence. Targeted proteomics analysis of the prioritized proteins in saliva, combined with machine-learning methods, highlights a peptide-based signature as the most powerful predictor to distinguish patients with and without lymph node metastasis. In summary, we identify a robust signature, which may enhance prognostic decisions in OSCC and better guide treatment to reduce tumor recurrence or lymph node metastasis.