University of Oulu

Carnielli, C., Macedo, C., De Rossi, T., Granato, D., Rivera, C., Domingues, R., Pauletti, B., Yokoo, S., Heberle, H., Busso-Lopes, A., Cervigne, N., Sawazaki-Calone, I., Meirelles, G., Marchi, F., Telles, G., Minghim, R., Ribeiro, A., Brandão, T., de Castro, G., González-Arriagada, W., Gomes, A., Penteado, F., Santos-Silva, A., Lopes, M., Rodrigues, P., Sundquist, E., Salo, T., da Silva, S., Alaoui-Jamali, M., Graner, E., Fox, J., Coletta, R., Paes Leme, A. (2018) Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer. Nature Communications, 9 (1), 3598. doi:10.1038/s41467-018-05696-2

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

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Author: Carnielli, Carolina Moretto1; Soares Macedo, Carolina Carneiro1,2; De Rossi, Tatiane1;
Organizations: 1CNPEM, Lab Espectrometria Massas, LNBio, BR-13083970 Campinas, SP, Brazil.
2Univ Estadual Campinas UNICAMP, Fac Odontol Piracicaba, Dept Diagnost Oral, BR-13414903 Piracicaba, SP, Brazil.
3Univ Sao Paulo, Inst Ciencias Matemat & Comp, BR-13560970 Sao Carlos, SP, Brazil.
4FMJ, Dept Morfol & Patol Basica, BR-13202550 Jundiai, SP, Brazil.
5Univ Estadual Oeste Parana, Fac Odontol, Ctr Ciencias Biol & Saude, BR-85819110 Cascavel, PR, Brazil.
6AC Camargo Canc Ctr, Ctr Int Pesquisa CIPE, BR-01508010 Sao Paulo, SP, Brazil.
7Inst Nacl Ciencia & Tecnol Oncogenom INCiTO, BR-01508010 Sao Paulo, SP, Brazil.
8Univ Estadual Campinas UNICAMP, Inst Comp, BR-13083852 Campinas, SP, Brazil.
9FMUSP, ICESP, Serv Odontol Oncol, BR-01246000 Sao Paulo, SP, Brazil.
10Univ Brasil, BR-15600000 Fernandopolis, SP, Brazil.
11ICESP, Inst Canc Estado Sao Paulo Octavio Frias de Olive, Serv Oncol Clin, BR-01246000 Sao Paulo, Brazil.
12Univ Valparaiso, Fac Odontol, Valparaiso 2340000, Chile.
13Waters Corp, BR-13070091 Campinas, SP, Brazil.
14Univ Oulu, Canc & Translat Med Res Unit, FI-90014 Oulu, Finland.
15Oulu Univ Hosp, Med Res Ctr, FI-90014 Oulu, Finland.
16Univ Helsinki, Dept Oral & Maxillofacial Dis, Clinicum, FI-00014 Helsinki, Finland.
17McGill Univ, Jewish Gen Hosp, Dept Otolaryngol Head & Neck Surg, Montreal, PQ H4A 3J1, Canada.
18McGill Univ, Lady Davis Inst Med Res, Fac Med, Montreal, PQ H3T 1E2, Canada.
19McGill Univ, Segal Canc Ctr, SMBD Jewish Gen Hosp, Dept Med,Fac Med, Montreal, PQ H3T 1E2, Canada.
20McGill Univ, Segal Canc Ctr, SMBD Jewish Gen Hosp, Dept Oncol,Fac Med, Montreal, PQ H3T 1E2, Canada.
21Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22903 USA.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.1 MB)
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Language: English
Published: Springer Nature, 2018
Publish Date: 2018-09-19


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.

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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 9
Article number: 3598
DOI: 10.1038/s41467-018-05696-2
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by FAPESP Grants 2009/54067-3, 2010/19278-0, 2013/16483-0, 2014/02288-0, 2016/07846-0, CNPq Grants 152619/2015-1, 470268/2013-1, 305432/2014-1. We acknowledge Prof. Dr. Tsai Siu Mui, CENA, USP for the use of the Leica Laser Microdissection Systems (FAPESP 2009/53998-3).
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