Verification of saliva proteins candidates for markers in OSCC and its correlation with prognosis

• Grant number: 15/12431-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2015
• Effective date (End): August 02, 2019
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Adriana Franco Paes Leme
• Grantee: Tatiane de Rossi Mazo
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovações (Brasil). Campinas , SP, Brazil
• Associated scholarship(s): 17/09526-6 - VERIFICATION OF SALIVA PROTEINS CANDIDATES FOR OSCC MARKERS AND THEIR CORRELATION WITH PROGNOSIS, BE.EP.DR

Abstract

The oral cancer with the highest incidence in the world is the squamous cell carcinoma (SCC), totaling more than 90% of all cases of cancer in the oral cavity. The most widely used prognostic factor is the clinical stage of the patient, based on the TNM classification (Malignant Tumors Classification). However, this classification system is not perfect, mainly because tumors with similar morphology and stage behave differently considering its different biological characteristics. Thus, the research of molecular markers involved in the development of human diseases has been the subject of intense research. The discovery that saliva are indicators of systemic disease, molecular profiles favored the development of a new outlook on noninvasive diagnosis: the diagnosis based on the saliva proteomics. In proteomics discovery studies, developed by our research group (1) differential abundance of 137 secreted protein was demonstrated by mass spectrometry in carcinoma cell line when compared to a noncancerous cell line (Kawahara et al. submitted to BMC Biology) and (2) the differential abundance of 44 proteins was found in the saliva of patients with SCC (Winck et al., submitted to Nature Scientific Reports). From these data, further study of proteomics-based targets, we find plenty of 14 proteins in saliva of patients with SCC and the differential abundance of 10 of these proteins was confirmed (Kawahara et al., submitted to the Journal of Proteome Research). However, despite these studies indicates potential candidates for markers, its correlation with the prognosis can not be performed due to the heterogeneous distribution of patients between the different staging. In addition, the high mortality rate compromised the calcutation of patient survival. Thus, the main objective of this project is the quantification of a panel of candidate proteins in the saliva of patients with SCC and the correlation with prognosis and risk of tumor regional metastasis in defined groups. The protein quantitation will be performed in the mass spectrometer LTQ Orbitrap Velos (Thermo Fisher Scientific) coupled with ultra performance liquid chromatography (LC-MS / MS). The candidate markers will be validated by immunohistochemistry (tissue microarray) to assess whether increased expression in saliva reflects the increased expression in SCC tissues and therefore is secreted by tissue or the increased expression is a response of patient organism to the presence of tumor. Proteins differentially abundant will be analyzed using specific software to obtain information about its interaction network, cellular localization and biological processes performed to assist in directing the functional studies of such molecules. It is expected that this project indicate a panel of marker proteins of SCC, contributing to the prognostic evaluation, the patient's risk profile and the possibility of recurrence and also lead to therapeutic intervention strategies.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RIVERA, CESAR; OLIVEIRA, ANA KARINA; PEREIRA COSTA, RUTE ALVES; DE ROSSI, TATIANE; PAES LEME, ADRIANA FRANCO. Prognostic biomarkers in oral squamous cell carcinoma: A systematic review. Oral Oncology, v. 72, p. 38-47, SEP 2017. (16/07846-0, 14/06485-9, 15/12431-1)

PALMIER, NATALIA RANGEL; PAES LEME, ADRIANA FRANCO; DE ROSSI, TATIANE; TELLES, GUILHERME PIMENTEL; MORAIS-FARIA, KARINA; KOWALSKI, LUIZ PAULO; MARTA, GUSTAVO NADER; BRANDAO, THAIS BIANCA; ARANY, PRAVEEN R.; MIGLIORATI, CESAR AUGUSTO; et al. Salivary alpha-1-antitrypsin and macrophage migration inhibitory factor may be potential prognostic biomarkers for oncologic treatment-induced severe oral mucositis. SUPPORTIVE CARE IN CANCER, v. 29, n. 6, p. 2939-2946, JUN 2021. (18/04657-8, 15/12431-1, 12/06138-1, 13/18402-8, 16/22862-2, 16/07846-0, 18/02233-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MAZO, Tatiane de Rossi. Verification of saliva proteins candidates for OSCC markers and their correlation with prognosis. 2019. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.