Background
The Warburg effect describes increased glucose uptake in cancer cells, and glucose
transporter proteins are overexpressed in many tumors. In this study, we evaluated
the expression of 14 SLC2A genes encoding glucose transporter proteins in papillary thyroid carcinoma patients.
Methods
Clinical information and gene expression data from 499 papillary thyroid carcinoma
patients were downloaded from The Cancer Genome Atlas database. Correlations between
SLC2 gene family (SLC2A1–14) mRNA expression levels and clinicopathologic factors were analyzed.
Results
There were 14 mortalities during follow-up (median, 21.6 months). Patient overall
mortality was associated with age ≥45 years, extrathyroidal extension, higher TNM
stage, and increased expression of SLC2A1, SLC2A3, and SLC2A14 mRNA. Greater SLC2A1, SLC2A3, and SLC2A14 expression was associated with increased mortality (odds ratio: 11.692, 95% confidence
interval: 3.362–36.938; odds ratio: 12.725, 95% confidence interval: 4.247–40.187;
and odds ratio: 13.768, 95% confidence interval: 4.208–61.710, respectively). Kaplan–Meier
survival analysis indicated that overall survival was shorter in patients with high
rather than low SCL2 expression (SLC2A1, P = .003; SLC2A3, P < .001; and SLC2A14, P < .001).
Conclusion
Upregulation of the SLC2A1, SLC2A3, and SLC2A14 genes was associated with increased mortality in papillary thyroid carcinoma patients,
and SLC2 gene expression levels are potentially useful prognostic indicators.
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References
- Otto Warburg's contributions to current concepts of cancer metabolism.Nat Rev Cancer. 2011; 11: 325-337
- The SLC2 (GLUT) family of membrane transporters.Mol Aspects Med. 2013; 34: 121-138
- Over-expression of facilitative glucose transporter genes in human cancer.Biochem Biophys Res Commun. 1990; 170: 223-230
- Immunohistochemical expression of glucose transporter Glut1 and cyclin D1 in breast carcinomas with negative lymph nodes.Eur J Gynaecol Oncol. 2003; 24: 544-546
- Clinical significance of glucose transporter 1 (GLUT1) expression in human breast carcinoma.Jpn J Cancer Res. 2002; 93: 1123-1128
- GLUT1 mRNA and protein expression in ovarian borderline tumors and cancer.Oncology. 2004; 66: 404-410
- GLUT1 expression is increased in hepatocellular carcinoma and promotes tumorigenesis.Am J Pathol. 2009; 174: 1544-1552
- Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival.Cancer. 1997; 80: 1046-1051
- Expression patterns of glucose transporter-1 gene and thyroid specific genes in human papillary thyroid carcinoma.Nucl Med Mol Imaging. 2014; 48: 91-97
- Expression of hypoxia-related glucose transporters GLUT1 and GLUT3 in benign, malignant and non-neoplastic thyroid lesions.Mol Med Rep. 2012; 6: 601-606
- Relationship between clinicopathological factors and fluorine-18-fluorodeoxyglucose uptake in patients with papillary thyroid cancer.Nucl Med Commun. 2011; 32: 690-698
- Integrated genomic characterization of papillary thyroid carcinoma.Cell. 2014; 159: 676-690
- Glucose transporter 1 expression, tumor proliferation, and iodine/glucose uptake in thyroid cancer with emphasis on poorly differentiated thyroid carcinoma.Clin Nucl Med. 2012; 37: 121-127
- Expression of the GLUT1 glucose transporter, p63 and p53 in thyroid carcinomas.Pathol Res Pract. 2006; 202: 759-765
- Comparison of 18F-fluorodeoxyglucose uptake with the expressions of glucose transporter type 1 and Na+/I- symporter in patients with untreated papillary thyroid carcinoma.Endocr Res. 2013; 38: 77-84
- Value of FDG PET in papillary thyroid carcinoma with negative 131I whole-body scan.J Nucl Med. 1999; 40: 986-992
- 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer; the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.Thyroid. 2016; 26: 1-133
- Differential expression of glucose transporters in normal and pathologic thyroid tissue.Thyroid. 2004; 14: 806-812
- Glucose transporter 1 gene expression is related to thyroid neoplasms with an unfavorable prognosis: an immunohistochemical study.Thyroid. 2002; 12: 747-754
- Tissue distribution of the human GLUT3 glucose transporter.Endocrinology. 1993; 132: 2538-2543
- GLUT14, a duplicon of GLUT3, is specifically expressed in testis as alternative splice forms.Genomics. 2002; 80: 553-557
- Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer.JAMA. 2013; 309: 1493-1501
- The BRAF(V600E) mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?.Clin Endocrinol (Oxf). 2014; 80: 899-904
- Sorafenib in advanced iodine-refractory differentiated thyroid cancer: efficacy, safety and exploratory analysis of role of serum thyroglobulin and FDG-PET.Clin Endocrinol (Oxf). 2013; 78: 760-767
- A pairwise chemical genetic screen identifies new inhibitors of glucose transport.Chem Biol. 2011; 18: 222-230
Article info
Publication history
Published online: November 11, 2016
Accepted:
April 10,
2016
Footnotes
Y.J.C. and J.W.Y. contributed equally to this study.
Supported by a multidisciplinary research grant-in-aid from the Seoul Metropolitan Government Seoul National University Boramae Medical Center (02-2015-8), and the Korean Health Technology R&D Project, Ministry of Health and Welfare (HI13C2164).
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
