title: Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells.
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.
authors.affiliation: Department of Pathology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Joao Paulo
authors.initials: JP
authors.lastname: Oliveira-Costa
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Alex Fiorini
authors.initials: AF
authors.lastname: de Carvalho
authors.affiliation: Department of Pathology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: da Giorgia Gobbi
authors.initials: da GG
authors.lastname: da Silveira
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Amaya
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
authors.forename: Kyoung-Joo Jenny
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Mabel Pinilla
authors.initials: MP
authors.lastname: Gigliola
authors.affiliation: Stefanie Spielman Comprehensive Breast Center, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Lustberg
authors.affiliation: Department of Anatomic Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Marcilei Eliza Cavicchioli
authors.initials: ME
authors.lastname: Buim
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Elisa Napolitano
authors.initials: EN
authors.lastname: Ferreira
authors.affiliation: Department of Head and Neck Surgery and Otorhinolaryngology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Chalmers
authors.affiliation: Department of Anatomic Pathology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE, A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: Department of Pathology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ribeiro-Silva
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000378:metabolism; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D014015:Tissue Banks; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D004268:DNA-Binding Proteins; C491257:HOXB9 protein, human; D018398:Homeodomain Proteins; C000608207:ZNF813 protein, human
keywords: PD-L1; Pathology Section; circulating tumor cells; gene expression; oral squamous cell carcinoma; survival