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

Carolina Moretto Carnielli, Carolina Carneiro Soares Macedo, Tatiane De Rossi, Daniela Campos Granato, César Rivera, Romênia Ramos Domingues, Bianca Alves Pauletti, Sami Yokoo, Henry Heberle, Ariane Fidelis Busso-Lopes, Nilva Karla Cervigne, Iris Sawazaki-Calone, Gabriela Vaz Meirelles, Fábio Albuquerque Marchi, Guilherme Pimentel Telles, Rosane Minghim, Ana Carolina Prado Ribeiro, Thaís Bianca Brandão, Gilberto de Castro, Wilfredo Alejandro González-ArriagadaAlexandre 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


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.

Original languageEnglish
Article number3598
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2018

Bibliographical note

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© 2018, The Author(s).


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