Abstract 4541: Malignant and non-malignant cells from primary tumor and lymph node metastasis ecosystems show different behavior for patient-associated protein signatures in head and neck cancer

Abstract

Abstract Although lymph node metastasis is the main prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC), the molecular signals involved in this process are poorly characterized and no molecular markers are currently used in clinical practice. Recently, cancer is being viewed as an ecosystem, in which tumor cells cooperate with each other and host cells in their microenvironment. Herein, we mapped the proteome of primary tumor and matched lymph node ecosystems, isolating malignant and non-malignant cells, to better understand the mechanisms underlying lymph node metastasis. For that, we used formalin-fixed paraffin-embedded (FFPE) primary tumors and paired lymph nodes from 27 HNSCC patients positive (N+, n=13) and negative (N0, n=14) for lymph node metastasis using laser microdissection combined with mass spectrometry-based proteomics. An average of 2,266 ± 216 proteins was identified in primary tumor and lymph node ecosystems. A hundred and five differentially abundant proteins from malignant cells in the primary site (N+ vs N0) were mainly involved in RNA stability and metabolism, while inflammation and splicing processes, respectively, were overrepresented in N+ vs N0 non-malignant cells signatures from primary tumor (N=33) and lymph node (N=13) sites (Student's t-test; P-value≤0.05), indicating particular lymph node metastasis signatures for each cell population. Interestingly, the protein pattern of malignant cells from the primary site and matched lymph nodes showed an individual patient-specific metastasis profile through hierarchical clustering analysis; however, the profile of non-malignant cells does not represent patient-specific subpopulations and grouped according to the site of isolation (primary tumor and lymph node microenvironment). Our data reveal potential protein signatures associated with prognosis in HNSCC, as well as a non-specificity of protein patterns from host non-malignant cells that can be related with the immunosurveillance failure. Financial support: FAPESP (Process number 2015/19191-6). Note: This abstract was not presented at the meeting. Citation Format: Ariane F. Busso-Lopes, César Rivera, Barbara P. Mello, Luisa L. Villa, Wilfredo González-Arriagada, Adriana F. Paes Leme. Malignant and non-malignant cells from primary tumor and lymph node metastasis ecosystems show different behavior for patient-associated protein signatures in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4541.