Glucose metabolism changes during the development and progression of oral tongue squamous cell carcinomas

Nakazato,Keiichiro; Mogushi,Kaoru; Kayamori,Kou; Tsuchiya,Maiko; Takahashi,Ken‑Ichiro; Sumino,Jun; Michi,Yasuyuki; Yoda,Tetsuya; Uzawa,Narikazu

doi:10.3892/ol.2019.10420

Glucose metabolism changes during the development and progression of oral tongue squamous cell carcinomas

Authors:
- Keiichiro Nakazato
- Kaoru Mogushi
- Kou Kayamori
- Maiko Tsuchiya
- Ken‑Ichiro Takahashi
- Jun Sumino
- Yasuyuki Michi
- Tetsuya Yoda
- Narikazu Uzawa
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Affiliations: Department of Maxillofacial Surgery, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113‑8549, Japan, Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Tokyo 113‑8421, Japan, Department of Oral Pathology, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113‑8549, Japan, Department of Oral Surgery, Toho University Faculty of Medicine, Toho University, Tokyo 143‑8540, Japan, Department of Oral and Maxillofacial Surgery II, Graduate School of Dentistry, Osaka University, Osaka 565‑0871, Japan
Published online on: May 30, 2019 https://doi.org/10.3892/ol.2019.10420
Pages: 1372-1380
Copyright: © Nakazato et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have revealed several genes involved in the carcinogenesis of oral cancer. However, the detailed mechanisms underlying this process are poorly understood. Previously, we established a database cataloging the transcriptional progression profile of oral carcinogenesis and identified several candidate genes with continuously increasing or decreasing expression, which specifically promote the transition of oral premalignant lesions to invasive carcinomas. In this study, using our microarray database, we attempted to determine significant genes that may contribute to metabolic alterations during oral carcinogenesis. After performing a literature survey, we focused on 15 candidate genes associated with glucose metabolism changes, particularly the tri‑carboxylic acid cycle, and investigated the mRNA‑expression status of these genes with our database. Only the solute carrier family 2 member 1 gene (also known as GLUT1), showed significantly increased mRNA expression during oral tumorigenesis. Immunohistochemical analysis confirmed that GLUT1 protein expression significantly increased during oral carcinogenesis. In addition, tumors with high expression of this protein significantly correlated with nodal status (P=0.002). Kaplan‑Meier survival curves clearly demonstrated the adverse impact of high GLUT1 protein expression on disease‑free survival (P=0.004). GLUT1 mRNA and protein expression increased in the order of normal mucosal tissues, epithelial dysplastic lesions and invasive carcinomas. Therefore, metabolic alterations, especially in glucose metabolism, occurred at the very early stage of development of oral malignancies. In addition, GLUT1 played a significant role in oral cancer, acquiring a malignant phenotype.

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