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Nat Commun. 2018 Sep 5;9(1):3598. doi: 10.1038/s41467-018-05696-2.

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

Author information

1
Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, 13083-970, SP, Brazil.
2
Departamento de Diagnóstico Oral, Faculdade de Odontologia de Piracicaba Universidade Estadual de Campinas (UNICAMP), Piracicaba, 13414-903, SP, Brazil.
3
Instituto de Ciências Matemáticas e de Computação, Universidade de São Paulo (USP), São Carlos, 13560-970, SP, Brazil.
4
Departamento de Morfologia e Patologia Básica, Faculdade de Medicina de Jundiaí (FMJ), Jundiaí, 13202-550, SP, Brazil.
5
Centro de Ciências Biológicas e da Saúde, Faculdade de Odontologia, Universidade Estadual do Oeste do Paraná, Cascavel, 85819- 110, PR, Brazil.
6
Centro Internacional de Pesquisa-CIPE - A.C.Camargo Cancer Center and Instituto Nacional de Ciência e Tecnologia em Oncogenômica (INCiTO), São Paulo, 01508-010, SP, Brazil.
7
Instituto de Computação, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-852, SP, Brazil.
8
Serviço de Odontologia Oncológica, Instituto do Câncer do Estado de São Paulo, ICESP-FMUSP, São Paulo, 01246-000, SP, Brazil.
9
Universidade Brasil, Fernandópolis, 15600-000, SP, Brazil.
10
Serviço de Oncologia Clínica, Instituto do Câncer do Estado de São Paulo, Octavio Frias de Oliveira, ICESP, São Paulo, 01246000, Brazil.
11
Facultad de Odontología, Universidad de Valparaíso, Valparaíso, 2340-000, Chile.
12
Waters Corporation, Campinas, 13070-091, SP, Brazil.
13
Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, FI-90014, Finland.
14
Medical Research Center, Oulu University Hospital, Oulu, FI-90014, Finland.
15
Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, FI-00014, Finland.
16
Department of Otolaryngology-Head and Neck Surgery, Jewish General Hospital, McGill University, Montréal, H4A 3J1, Canada.
17
Lady Davis Institute for Medical Research and Segal Cancer Center, SMBD Jewish General Hospital, Departments of Medicine and Oncology, Faculty of Medicine, McGill University, Montreal, H3T 1E2, Canada.
18
Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, 22903, VA, USA.
19
Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, 13083-970, SP, Brazil. adriana.paesleme@lnbio.cnpem.br.

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.

PMID:
30185791
PMCID:
PMC6125363
DOI:
10.1038/s41467-018-05696-2
[Indexed for MEDLINE]
Free PMC Article

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