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

Author(s):Show less -

Carnielli, Carolina Moretto ^[1] ; Soares Macedo, Carolina Carneiro ^{[1, 2]} ; De Rossi, Tatiane ^[1] ; Granato, Daniela Campos ^[1] ; Rivera, Cesar ^{[1, 2]} ; Domingues, Romenia Ramos ^[1] ; Pauletti, Bianca Alves ^[1] ; Yokoo, Sami ^[1] ; Heberle, Henry ^[3] ; Busso-Lopes, Ariane Fidelis ^[1] ; Cervigne, Nilva Karla ^{[2, 4]} ; Sawazaki-Calone, Iris ^[5] ; Meirelles, Gabriela Vaz ^[1] ; Marchi, Fabio Albuquerque ^{[6, 7]} ; Telles, Guilherme Pimentel ^[8] ; Minghim, Rosane ^[3] ; Prado Ribeiro, Ana Carolina ^{[9, 10]} ; Brandao, Thais Bianca ^[9] ; Castro, Jr., Gilberto de ^[11] ; Alejandro Gonzalez-Arriagada, Wilfredo ^[12] ; Gomes, Alexandre ^[13] ; Penteado, Fabio ^[13] ; Santos-Silva, Alan Roger ^[2] ; Lopes, Marcio Ajudarte ^[2] ; Rodrigues, Priscila Campioni ^{[14, 15]} ; Sundquist, Elias ^{[14, 15]} ; Salo, Tuula ^{[14, 15, 16]} ; da Silva, Sabrina Daniela ^{[17, 18, 19, 20]} ; Alaoui-Jamali, Moulay A. ^{[17, 18, 19]} ; Graner, Edgard ^[2] ; Fox, Jay W. ^[21] ; Della Coletta, Ricardo ^[2] ; Paes Leme, Adriana Franco ^[1]

Affiliation:Show less -

^[1] CNPEM, Lab Espectrometria Massas, LNBio, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas UNICAMP, Fac Odontol Piracicaba, Dept Diagnost Oral, BR-13414903 Piracicaba, SP - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Matemat & Comp, BR-13560970 Sao Carlos, SP - Brazil

^[4] FMJ, Dept Morfol & Patol Basica, BR-13202550 Jundiai, SP - Brazil

^[5] Univ Estadual Oeste Parana, Fac Odontol, Ctr Ciencias Biol & Saude, BR-85819110 Cascavel, PR - Brazil

^[6] AC Camargo Canc Ctr, Ctr Int Pesquisa CIPE, BR-01508010 Sao Paulo, SP - Brazil

^[7] Inst Nacl Ciencia & Tecnol Oncogenom INCiTO, BR-01508010 Sao Paulo, SP - Brazil

^[8] Univ Estadual Campinas UNICAMP, Inst Comp, BR-13083852 Campinas, SP - Brazil

^[9] FMUSP, ICESP, Serv Odontol Oncol, BR-01246000 Sao Paulo, SP - Brazil

^[10] Univ Brasil, BR-15600000 Fernandopolis, SP - Brazil

^[11] ICESP, Inst Canc Estado Sao Paulo Octavio Frias de Olive, Serv Oncol Clin, BR-01246000 Sao Paulo - Brazil

^[12] Univ Valparaiso, Fac Odontol, Valparaiso 2340000 - Chile

^[13] Waters Corp, BR-13070091 Campinas, SP - Brazil

^[14] Univ Oulu, Canc & Translat Med Res Unit, FI-90014 Oulu - Finland

^[15] Oulu Univ Hosp, Med Res Ctr, FI-90014 Oulu - Finland

^[16] Univ Helsinki, Dept Oral & Maxillofacial Dis, Clinicum, FI-00014 Helsinki - Finland

^[17] McGill Univ, Lady Davis Inst Med Res, Fac Med, Montreal, PQ H3T 1E2 - Canada

^[18] McGill Univ, Segal Canc Ctr, SMBD Jewish Gen Hosp, Dept Med, Fac Med, Montreal, PQ H3T 1E2 - Canada

^[19] McGill Univ, Segal Canc Ctr, SMBD Jewish Gen Hosp, Dept Oncol, Fac Med, Montreal, PQ H3T 1E2 - Canada

^[20] McGill Univ, Jewish Gen Hosp, Dept Otolaryngol Head & Neck Surg, Montreal, PQ H4A 3J1 - Canada

^[21] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22903 - USA

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 9, SEP 5 2018.
• Web of Science Citations: 13

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. (AU)

• 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 Opportunities: Regular Research Grants
• 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 Opportunities: Multi-user Equipment Program
• FAPESP's process: 13/16483-0 - Study of protein composition in the invasion area of squamous cell carcinoma by proteomics based on mass spectrometry
• Grantee: Carolina Moretto Carnielli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/19278-0 - Study of regulation of ADAMs in oral cancer
• Grantee: Adriana Franco Paes Leme
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 09/53998-3 - Acquisition of a laser capture microdissection platform for application in cell and molecular biology studies
• Grantee: Tsai Siu Mui
• Support Opportunities: Multi-user Equipment Program