Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer

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Busso-Lopes, Ariane F. ; Neves, Leandro X. ; Camara, Guilherme A. ; Granato, Daniela C. ; Pretti, Marco Antonio M. ; Heberle, Henry ; Patroni, Fabio M. S. ; Sa, Jamile ; Yokoo, Sami ; Rivera, Cesar ; Domingues, Romenia R. ; Normando, Ana Gabriela C. ; De Rossi, Tatiane ; Mello, Barbara P. ; Galdino, Nayane A. L. ; Pauletti, Bianca A. ; Lacerda, Pammela A. ; Rodrigues, Andre Afonso N. ; Casarim, Andre Luis M. ; De Lima-Souza, Reydson A. ; Damas, Ingrid I. ; Mariano, Fernanda, V ; Gollob, Kenneth J. ; Medina, Tiago S. ; Cervigne, Nilva K. ; Prado-Ribeiro, Ana Carolina ; Brandao, Thais Bianca ; Villa, Luisa L. ; Uno, Miyuki ; Boroni, Mariana ; Kowalski, Luiz Paulo ; Gonzalez-Arriagada, Wilfredo Alejandro ; Leme, Adriana F. Paes

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 13, n. 1, p. 24-pg., 2022-11-07.

Abstract

The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures. The biological understanding of poor prognosis associated with lymph node metastasis in head and neck cancer (HNC) remains crucial. Here, a proteomic characterisation of 140 multisite samples from a 59-HNC patient cohort and machine learning reveals potential biomarkers and metastasis related signatures. (AU)

• FAPESP's process: 19/21815-9 - Multiplex N-terminomics analysis of cardiomyocyte secretome based on MMP-2 and ADAM17 activity using TMT-TAILS quantitative proteomics
• Grantee: Ariane Fidelis Busso Lopes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/19191-6 - Proteomic analysis of the invasive front in head and neck squamous cell carcinomas with regional metastasis
• Grantee: Ariane Fidelis Busso Lopes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/50612-8 - An integrated approach to explore a novel paradigm for biofuel production from lignocellulosic feedstocks
• Grantee: Telma Teixeira Franco
• Support Opportunities: Research Projects - Thematic Grants
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• Grantee: Tsai Siu Mui
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 18/18496-6 - The role of alcohol treated-extracellular vesicles in oral cells transformation
• Grantee: Adriana Franco Paes Leme
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/00417-3 - System biology techniques applied to the agriculture: transcriptomes and interactomes analyses
• Grantee: Marcelo Mendes Brandao
• Support Opportunities: Research Grants - Young Investigators 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: 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: 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