Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

Abstract

Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative real-time PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p < 0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p < 0.05). SLC2A3 was related to grade and invasion type (p < 0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p < 0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.

Transcriptomic changes in human renal proximal tubular cells revealed under hypoxic conditions by RNA sequencing

“…All DEGs were classified into GO and KEGG categories to provide an overview of their biological functions and associated biochemical pathways. Many studies have shown the expression of individual hypoxia-related genes in different cells (28)(29)(30). In the present study, our analysis indicated that the upregulated genes were highly enriched in ECM organization (GO:0030198), protein binding (GO:0005515), extra ventricular cardiac muscle cell differentiation (GO:0055012), diphosphotransferase activity (GO:0016778) and the cytoplasm (GO:0005737).…”

Integrated Analysis of Long Noncoding RNA and mRNA Expression Profile in Advanced Laryngeal Squamous Cell Carcinoma

“…Intratumoral hypoxia is a common feature of solid malignancies, including LSCC. Indeed, HIF1a has been well studied in cancer progression and is implicated in the malignancy phenotype of LSCC [37–38]. Phosphoinositide-3-kinase regulatory subunit 1(PIK3R1) binds, stabilizes and inhibits the PI3K p110 catalytic subunit [39].…”

Individualized outcome prognostication for patients with laryngeal cancer

“…Accepted standards for tumor staging and oncologic prognostication continue to be helpful in confronting these challenges and guiding decision making . However, in order to further individualize treatment selections that enhance survival and minimize morbidity, more sophisticated methods that successfully capitalize on emerging discoveries related to tumor biology/genomics and patient factors are mandatory . Treatment decision making is particularly complex for laryngeal cancer because of the various treatment options available and the differing short‐term and long‐term functional consequences that affect quality of life and survival.…”

“…6,7 However, in order to further individualize treatment selections that enhance survival and minimize morbidity, more sophisticated methods that successfully capitalize on emerging discoveries related to tumor biology/genomics and patient factors are mandatory. 8,9 Treatment decision making is particularly complex for laryngeal cancer because of the various treatment options available and the differing short-term and long-term functional consequences that affect quality of life and survival. The management of laryngeal cancer has experienced substantial evolution, primarily driven by the implementation of chemotherapeutic modalities and novel organ-preservation strategies.…”