title: HOX genes: potential candidates for the progression of laryngeal squamous cell carcinoma.
abstract: Laryngeal squamous cell carcinoma (LSCC) is a very aggressive cancer, considered to be a subtype of the head and neck squamous cell carcinoma (HNSCC). Despite significant advances in the understanding and treatment of cancer, prognosis of patients with LSCC has not improved recently. In the present study, we sought to understand better the genetic mechanisms underlying LSCC development. Thirty-two tumor samples were collected from patients undergoing surgical resection of LSCC. The samples were submitted to whole-genome cDNA microarray analysis aiming to identify genetic targets in LSCC. We also employed bioinformatic approaches to expand our findings using the TCGA database and further performed functional assays, using human HNSCC cell lines, to evaluate viability, cell proliferation, and cell migration after silencing of selected genes. Eight members of the homeobox gene family (HOX) were identified to be overexpressed in LSCC samples when compared to normal larynx tissue. Quantitative RT-PCR analysis validated the overexpression of HOX gene family members in LSCC. Receiver operating characteristic (ROC) statistical method curve showed that the expression level of seven members of HOX gene family can distinguish tumor from nontumor tissue. Correlation analysis of clinical and gene expression data revealed that HOXC8 and HOXD11 genes were associated with the differentiation degree of tumors and regional lymph node metastases, respectively. Additionally, siRNA assays confirmed that HOXC8, HOXD10, and HOXD11 genes might be critical for cell colony proliferation and cell migration. According to our findings, several members of the HOX genes were overexpressed in LSCC samples and seem to be required in biological processes involved in tumor development. This suggests that HOX genes might play a critical role in the physiopathology of LSCC tumors.
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.|National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.
authors.forename: Rafaela
authors.initials: R
authors.lastname: de Barros E Lima Bueno
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.|National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.
authors.forename: Anelisa
authors.initials: A
authors.lastname: Ramão
authors.affiliation: Department of Technology, College of Agriculture and Veterinary Sciences, UNESP, Jaboticabal, SP, CEP: 14884-900, Brazil.
authors.forename: Daniel Guariz
authors.initials: DG
authors.lastname: Pinheiro
authors.affiliation: National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.|Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.
authors.forename: Cleidson Padua
authors.initials: CP
authors.lastname: Alves
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.
authors.forename: Vinicius
authors.initials: V
authors.lastname: Kannen
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.|National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.|Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.
authors.forename: Luiza Ferreira
authors.initials: LF
authors.lastname: de Araújo
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.|National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.
authors.forename: Bruna Rodrigues
authors.initials: BR
authors.lastname: Muys
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.|National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.|Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.
authors.forename: Aline Simoneti
authors.initials: AS
authors.lastname: Fonseca
authors.affiliation: National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.|Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.
authors.forename: Jessica Rodrigues
authors.initials: JR
authors.lastname: Plaça
authors.affiliation: National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil.
authors.forename: Rodrigo Alexandre
authors.initials: RA
authors.lastname: Panepucci
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.
authors.forename: Fabiano P
authors.initials: FP
authors.lastname: Saggioro
authors.affiliation: Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil.
authors.forename: Rui Celso M
authors.initials: RC
authors.lastname: Mamede
authors.affiliation: University of Centro-Oeste, Rua Padre Salvador, 875, Santa Cruz, Guarapuava, PR, CEP 85015-430, Brazil.
authors.forename: David Livingstone Alves
authors.initials: DL
authors.lastname: Figueiredo
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, CEP: 14049-900, Brazil. wilsonjr@usp.br.|National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil. wilsonjr@usp.br.|Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil. wilsonjr@usp.br.|Centro Regional de Hemoterapia de Ribeirão Preto, Rua Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, SP, CEP: 14051-140, Brazil. wilsonjr@usp.br.
authors.forename: Wilson Araújo
authors.initials: WA
authors.lastname: Silva
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: Cell migration; Gene regulation; HOX genes; Larynx squamous cell carcinoma