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From discovery to validation of prognostic candidates for oral cancer in liquid biopsies


Squamous Cell Carcinoma (SCC) is the most common type of Oral Cancer (OSCC) and is a malignity derived from the squamous stratified epithelium of the oral mucosa. Regardless of the advances in the treatment of OSCC along the years, the rate of survival is very low, with 50% of the advanced cases dying in the period of 5 years. Besides, the prognosis and treatment strategies are defined mostly based on TNM classification. Thus, the identification of biological signatures may complement the clinical decision. Discovery based proteomics combined with targeted proteomics, associated with Computational Biology are robust techniques currently used to identify, quantify and classify prognostic signatures in different types of cancer. Besides, the original, recent and promising results from the group, especially when evaluating liquid biopsies, reinforce the potential of these strategies. Considering that the most common prognostic factor in cases of patients with SCC involves the lymph node metastasis, this project aims in the discovery phase to (i) characterize the proteins (panel of signatures) with prognosis meaning, extracted from (1) saliva and (2) tear fluid of oral SCC patients and from healthy control individuals; in a second phase (ii) verify signatures, also in plasma, and in a small cohort of patients, through targeted proteomics; and on a third phase (iii) validate the signatures, in a large cohort of patients, for clinical application through targeted proteomics, Immunohistochemistry (IHC) and Enzyme-Linked Immunosorbent Assays (ELISA). The strategy proposed in this project is very promising for the scientific community, in the field of Head and Neck Carcinoma, as well as for proteomics based in mass spectrometry, as demonstrated by the recent work from the group that has been recognized and published in Nature Communications (Carnielli, Macedo, De Rossi, Granato et al., 2018). It is expected that the signature with prognostic value provided from the analysis of liquid biopsies may improve the clinical decision for treatment modalities and, with that, improve the survival and quality of life of the patients. (AU)

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Scientific publications (7)
(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)
SA, JAMILE DE OLIVEIRA; TRINO, LUCIANA DANIELE; OLIVEIRA, ANA KARINA; BUSSO LOPES, ARIANE FIDELIS; GRANATO, DANIELA CAMPOS; COSTA NORMANDO, ANA GABRIELA; SANTOS, ERISON SANTANA; NEVES, LEANDRO XAVIER; CARNIELLI, CAROLINA MORETTO; PAES LEME, ADRIANA FRANCO. Proteomic approaches to assist in diagnosis and prognosis of oral cancer. EXPERT REVIEW OF PROTEOMICS, v. 18, n. 4, p. 261-284, . (18/11958-4, 19/21815-9, 18/18496-6, 18/12194-8, 19/18751-9, 19/09692-9, 18/02180-0, 18/15535-0, 18/15728-3, 16/19337-3)
GRANATO, DANIELA C.; NEVES, LEANDRO X.; TRINO, LUCIANA D.; CARNIELLI, CAROLINA M.; LOPES, ARIANE F. B.; YOKOO, SAMI; PAULETTI, BIANCA A.; DOMINGUES, ROMENIA R.; SA, JAMILE O.; PERSINOTI, GABRIELLA; et al. Meta-omics analysis indicates the saliva microbiome and its proteins associated with the prognosis of oral cancer patients. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1869, n. 8, . (18/18496-6, 18/02180-0, 16/07846-0, 19/18751-9, 19/21815-9, 09/54067-3, 18/11958-4, 15/50590-4, 18/12194-8, 18/15728-3, 14/06485-9, 18/15535-0, 10/19278-0)
ZANDONADI, FLAVIA S.; YOKOO, SAMI; GRANATO, DANIELA CAMPOS; RIVERA, CESAR; SOARES MACEDO, CAROLINA CARNEIRO; SOARES, CIRO DANTAS; CARNIELLI, CAROLINA MORETTO; DOMINGUES, ROMENIA RAMOS; PAULETTI, BIANCA A.; CONSONNI, SILVIO ROBERTO; et al. Follistatin-related protein 1 interacting partner of Syndecan-1 promotes an aggressive phenotype on Oral Squamous cell carcinoma (OSCC) models. JOURNAL OF PROTEOMICS, v. 254, p. 13-pg., . (13/02257-9, 18/18496-6, 16/50005-7, 18/15535-0, 16/07846-0, 19/18751-9, 09/54067-3, 10/19278-0)
E COSTA, RUTE A. P.; GRANATO, DANIELA C.; TRINO, LUCIANA D.; YOKOO, SAMI; CARNIELLI, CAROLINA M.; KAWAHARA, REBECA; DOMINGUES, ROMENIA R.; PAULETTI, BIANCA ALVES; NEVES, LEANDRO XAVIER; SANTANA, ALINE G.; et al. ADAM17 cytoplasmic domain modulates Thioredoxin-1 conformation and activity. REDOX BIOLOGY, v. 37, . (16/01528-7, 18/12194-8, 19/18751-9, 18/18496-6, 09/54067-3, 18/15535-0, 14/23888-0, 16/07846-0, 16/24664-3, 14/06485-9, 10/19278-0)
PAULETTI, BIANCA A. .; GRANATO, DANIELA C.; CARNIELLI, CAROLINA M.; CAMARA, GUILHERME A.; NORMANDO, ANA GABRIELA C.; TELLES, GUILHERME P.; LEME, ADRIANA F. PAES. Typic: A Practical and Robust Tool to Rank Proteotypic Peptides for Targeted Proteomics. JOURNAL OF PROTEOME RESEARCH, v. N/A, p. 7-pg., . (19/18751-9, 19/09692-9, 18/18496-6, 18/15535-0, 19/14828-7)
NORMANDO, ANA GABRIELA COSTA; DOS SANTOS, ERISON SANTANA; SA, JAMILE DE OLIVEIRA; BUSSO-LOPES, ARIANE FIDELIS; DE ROSSI, TATIANE; PATRONI, FABIO MALTA DE SA; GRANATO, DANIELA CAMPOS; GUERRA, ELIETE NEVES SILVA; SANTOS-SILVA, ALAN ROGER; LOPES, MARCIO AJUDARTE; et al. A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia. FRONTIERS IN ORAL HEALTH, v. 4, p. 15-pg., . (22/04490-1, 19/18751-9, 21/03319-4, 19/09692-9, 18/15535-0, 21/05965-0, 18/18496-6)
PAULETTI, BIANCA A.; GRANATO, DANIELA C.; CARNIELLI, CAROLINA M.; CAMARA, GUILHERME A.; NORMANDO, ANA GABRIELA C.; TELLES, GUILHERME P.; LEME, ADRIANA F. PAES. Typic: A Practical and Robust Tool to Rank Proteotypic Peptides for Targeted Proteomics. JOURNAL OF PROTEOME RESEARCH, v. 22, n. 2, p. 7-pg., . (19/09692-9, 18/02180-0, 19/14828-7, 18/18496-6, 18/15535-0, 19/18751-9)

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