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Tumor Biology

, Volume 37, Issue 11, pp 15087–15096 | Cite as

HOX genes: potential candidates for the progression of laryngeal squamous cell carcinoma

  • Rafaela de Barros e Lima Bueno
  • Anelisa Ramão
  • Daniel Guariz Pinheiro
  • Cleidson Padua Alves
  • Vinicius Kannen
  • Achim A Jungbluth
  • Luiza Ferreira de Araújo
  • Bruna Rodrigues Muys
  • Aline Simoneti Fonseca
  • Jessica Rodrigues Plaça
  • Rodrigo Alexandre Panepucci
  • Luciano Neder
  • Fabiano P Saggioro
  • Rui Celso M. Mamede
  • David Livingstone Alves Figueiredo
  • Wilson Araújo SilvaJr
Original Article

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.

Keywords

Larynx squamous cell carcinoma Gene regulation HOX genes Cell migration 

Notes

Acknowledgments

We thank Amélia Goes de Araújo and Patrícia Vianna Bonini Palma for the technical support at Flow Cytometry Core at National Institute of Science and Technology in Stem Cell and Cell Therapy for the technical support. We also thank Josane de Freitas Sousa for the critical review of the manuscript final version. This work was supported by grant no. 140427/2010-4, National Counsel of Technological and Scientific Development (CNPq); grant no. 559809/2009-3 CNPq/GENOPROT; and grant nos. 2012/00588-5 and #2013/08135-2, São Paulo Research Foundation (FAPESP).

Compliance with ethical standards

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Ribeirão Preto Medical School, University of São Paulo (USP) (Proc. No. 9371/2003). All patients underwent surgical resection at the Head and Neck Surgery Division of the Department of Ophthalmology, Otorhinolaryngology and Head & Neck of Ribeirão Preto Medical School, USP, and an informed consent was obtained from patients before surgery.

Conflicts of interest

None.

Supplementary material

13277_2016_5356_MOESM1_ESM.docx (32.1 mb)
ESM 1 (DOCX 32879 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Rafaela de Barros e Lima Bueno
    • 1
    • 2
  • Anelisa Ramão
    • 1
    • 2
  • Daniel Guariz Pinheiro
    • 3
  • Cleidson Padua Alves
    • 2
    • 4
  • Vinicius Kannen
    • 5
  • Achim A Jungbluth
    • 6
  • Luiza Ferreira de Araújo
    • 1
    • 2
    • 4
  • Bruna Rodrigues Muys
    • 1
    • 2
  • Aline Simoneti Fonseca
    • 1
    • 2
    • 4
  • Jessica Rodrigues Plaça
    • 2
    • 4
  • Rodrigo Alexandre Panepucci
    • 2
  • Luciano Neder
    • 5
  • Fabiano P Saggioro
    • 5
  • Rui Celso M. Mamede
    • 7
  • David Livingstone Alves Figueiredo
    • 8
  • Wilson Araújo SilvaJr
    • 1
    • 2
    • 4
    • 9
  1. 1.Department of Genetics, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  2. 2.National Institute of Science and TechnologyStem Cell and Cell Therapy and Center for Cell Based TherapyRibeirão PretoBrazil
  3. 3.Department of Technology, College of Agriculture and Veterinary SciencesUNESPJaboticabalBrazil
  4. 4.Center for Integrative Systems BiologyCISBi, NAP/USPRibeirão PretoBrazil
  5. 5.Department of Pathology, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  6. 6.Department of PathologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  7. 7.Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  8. 8.University of Centro-OesteGuarapuavaBrazil
  9. 9.Centro Regional de Hemoterapia de Ribeirão PretoRibeirão PretoBrazil

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