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Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells
Authors:Joao Paulo Oliveira-Costa  Alex Fiorini de Carvalho  Giorgia Gobbi da Silveira  Peter Amaya  Yongqi Wu  Kyoung-Joo Jenny Park  Mabel Pinilla Gigliola  Maryam Lustberg  Marcilei Eliza Cavicchioli Buim  Elisa Napolitano Ferreira  Luiz Paulo Kowalski  Jeffrey J. Chalmers  Fernando Augusto Soares  Dirce Maria Carraro  Alfredo Ribeiro-Silva
Abstract:Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity and has been associated with poor prognosis. Scarce prognostic markers are available for guiding treatment and/or sub-classifying patients. This study aims to identify biomarkers by searching for genes whose expression is increased or decreased during tumor progression (through T1 to T4 stages). Thirty-six samples from all tumor size stages (from T1 to T4) were analyzed using cDNA microarrays. Selected targets were analyzed by immunohistochemistry and in circulating tumor cells by immunofluorescence and Nanostring. Correlation was shown between PD-L1 and tumor size and lymph node metastasis, HOXB9 and tumor size, BLNK and perineural invasion, and between ZNF813 and perineural invasion. PD-L1 positivity was an independent prognostic factor in this cohort (p = 0.044, HH = 0.426). In CTCs from patients with locally advanced OSCC, we found a strong cytoplasmatic expression of PD-L1. PD-L1 is a ligand of PD-1 and is believed to limit T cell activity in inflammatory responses and limit autoimmune diseases. We demonstrated an important role for PD-L1 in primary tumors according to tumor size, and in disease specific survival. Therefore, we could further determine individuals with PD-L1+ CTCs, and possibly follow treatment using CTCs.
Keywords:PD-L1   oral squamous cell carcinoma   gene expression   circulating tumor cells   survival
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