Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells

// Joao Paulo Oliveira-Costa 1 , Alex Fiorini de Carvalho 2 , Giorgia Gobbi da Silveira 1 , Peter Amaya 3 , Yongqi Wu 3 , Kyoung-Joo Jenny Park 3 , Mabel Pinilla Gigliola 2 , Maryam Lustberg 4 , Marcilei Eliza Cavicchioli Buim 5 , Elisa Napolitano Ferreira 2 , Luiz Paulo Kowalski 6 , Jeffrey J. Chalmers 3 , Fernando Augusto Soares 5 , Dirce Maria Carraro 2 , Alfredo Ribeiro-Silva 1 1 Department of Pathology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil 2 Laboratory of Genomics and Molecular Biology, CIPE, A.C. Camargo Cancer Center, Sao Paulo, Brazil 3 William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA 4 Stefanie Spielman Comprehensive Breast Center, Wexner Medical Center, The Ohio State University, Columbus, OH, USA 5 Department of Anatomic Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil 6 Department of Head and Neck Surgery and Otorhinolaryngology, A.C. Camargo Cancer Center, Sao Paulo, Brazil Correspondence to: Joao Paulo Oliveira-Costa, e-mail: oliveiracostajp@gmail.com Keywords: PD-L1, oral squamous cell carcinoma, gene expression, circulating tumor cells, survival Received: February 23, 2015      Accepted: May 05, 2015      Published: May 15, 2015 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.