Prognostic implications of CD44, NANOG, OCT4, and BMI1 expression in tongue squamous cell carcinoma

Maria Fernanda Setúbal Destro Rodrigues; Flávia Caló de Aquino Xavier; Nathália Paiva Andrade; Camila Lopes; Lucyene Miguita Luiz; Bruno Tavares Sedassari; Ana Melissa Ccopa Ibarra; Rossana Verónica Mendoza López; Claudia Kliemann Schmerling; Raquel Ajub Moyses; Eloiza Elena Tajara da Silva; Fabio Daumas Nunes

doi:10.1002/hed.25158

Prognostic implications of CD44, NANOG, OCT4, and BMI1 expression in tongue squamous cell carcinoma

Head Neck. 2018 Aug;40(8):1759-1773. doi: 10.1002/hed.25158. Epub 2018 Apr 1.

Authors

Affiliations

¹ Oral and Maxillofacial Pathology Department, School of Dentistry, University of São Paulo, São Paulo, Brazil.
² Postgraduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University (UNINOVE), São Paulo, São Paulo, Brazil.
³ Laboratory of Oral Surgical Pathology, School of Dentistry, Federal University of Bahia, Salvador, Brazil.
⁴ Department of Molecular Biology, São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo, Brazil.
⁵ Surgery Department, School of Medicine, University of São Paulo (USP), São Paulo, Brazil.

PMID: 29607565
DOI: 10.1002/hed.25158

Abstract

Background: Tongue squamous cell carcinoma (SCC) contains a cell subpopulation referred to as cancer stem cells (CSCs), which are responsible for tumor growth, metastasis, and resistance to chemotherapy and radiotherapy. The CSC markers have been used to isolate these cells and as biomarkers to predict overall survival.

Methods: The CSC markers CD44, NANOG, OCT4, and BMI1 were investigated using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry and correlated with clinicopathological parameters.

Results: The CD44 overexpression was associated with disease-related death (P = 0.02) and worst prognosis. NANOG was upregulated in nontumoral margins and associated with T1/T2 classification, lymph node metastasis, and worst prognosis. OCT4 was associated with lymph node metastasis and worst overall survival. BMI1 and CD44v3 were overexpressed in tongue SCC. Coexpression of CD44⁺⁺ /NANOG⁺⁺ was associated with worst overall survival when compared with patients with CD44^-/+ /NANOG^-/+ .

Conclusion: The CSC markers might play an important role not only in CSC trait acquisition but also in tongue SCC development and progression.

Keywords: cancer stem cell; clinicopathological features; prognosis; stem cell markers; tongue squamous cell carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers, Tumor / metabolism
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / mortality*
Epithelial Cells / metabolism
Female
Humans
Hyaluronan Receptors / genetics
Hyaluronan Receptors / metabolism*
Immunohistochemistry
Keratinocytes / metabolism
Lymphatic Metastasis
Male
Nanog Homeobox Protein / genetics
Nanog Homeobox Protein / metabolism*
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism*
Polycomb Repressive Complex 1 / genetics
Polycomb Repressive Complex 1 / metabolism*
Prognosis
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tongue Neoplasms / metabolism
Tongue Neoplasms / mortality*
Up-Regulation

Substances

BMI1 protein, human
Biomarkers, Tumor
CD44 protein, human
Hyaluronan Receptors
Nanog Homeobox Protein
Octamer Transcription Factor-3
POU5F1 protein, human
RNA, Messenger
Polycomb Repressive Complex 1