Glucose metabolism changes during the development and progression of oral tongue squamous cell carcinomas
Glucose metabolism changes during the development and progression of oral tongue squamous cell carcinomas
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DOI：
10.3892/ol.2019.10420
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发表时间：
2019-08-01
期刊：
影响因子：
2.9
通讯作者：
Uzawa, Narikazu
中科院分区：
文献类型：
--
作者：
Nakazato, Keiichiro;Mogushi, Kaoru;Uzawa, Narikazu
以前的研究已经揭示了几个基因参与口腔癌的致癌作用。然而，这一过程背后的详细机制知之甚少。在此之前，我们建立了一个数据库编目的口腔癌发生的转录进展概况，并确定了几个候选基因的表达不断增加或减少，特别是促进口腔癌前病变的过渡到浸润性癌。在这项研究中，使用我们的微阵列数据库，我们试图确定在口腔癌发生过程中可能导致代谢改变的重要基因。在进行了文献调查后，我们集中在15个候选基因与葡萄糖代谢的变化，特别是三羧酸循环，并调查这些基因的mRNA表达状态与我们的数据库。只有溶质载体家族2成员1基因（也称为GLUT 1）在口腔肿瘤发生过程中表现出显著增加的mRNA表达。免疫组化分析证实，GLUT 1蛋白表达显着增加，在口腔癌的发生。此外，这种蛋白高表达的肿瘤与淋巴结状态显著相关（P=0.002）。Kaplan-Meier生存曲线清楚地显示了高GLUT 1蛋白表达对无病生存的不利影响（P=0.004）。GLUT 1 mRNA和蛋白表达在正常黏膜组织、上皮不典型增生和浸润性癌中依次增高。因此，代谢的改变，特别是在葡萄糖代谢，发生在口腔恶性肿瘤的发展非常早期的阶段。此外，GLUT 1在口腔癌中发挥重要作用，获得恶性表型。
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.