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Vertika Rai
Surajit Bose
Gopeshwar Mukherjee
Rakshith Shetty
Hasina Perveen
Suchismita Mukherjee
Dipankar Das
Debayan Chakraborty
Riya Sarkar
Dipanjan Bhattacharjee


Glucose transporter 1, Hexokinase 2, Oral submucous fibrosis, Oxidative stress


Objectives:. The objective of the present study was to assess the clinical correlation with biochemical changes in serum with histological findings in the tissue and serum of oral submuous fibrosis subjects  and to explore the possibilities of blood-based biomarkers for the disease leading to oxidative stress

Methods: This study was conducted on serum and tissue sample of Oral Submucous fibrosis (OSF)  (n = 20) compared with the healthy group (n = 20). Tissues were stained with special histochemical stains for carbohydrates [Periodic acid Schiff (PAS)], Lipids [Sudan IV], Collagen [Van Gieson’s (VG Stain)] for histochemical feature analysis. The expression of glucose metabolism-related proteins glucose transporter 1 and hexokinase 2  in tissue was validated by western blot technique. A commercially available ELISA Kit quantified glucose transporter1(GLUT1)and hexokinase2(HK2) molecule in serum.

Results: Histochemical analysis by special stains supported the evidence of altered metabolic activity in tissues. Detail study of metabolic protein by western blot showed that the glucose transporter 1 and hexokinase 2 expression in oral submucous fibrosis tissues were significantly higher compared to normal. Further in serum elevated level of glucose transporter 1 and hexokinase showed that the serum expression followed a trend similar to the expression pattern observed and in tissues.

Conclusion:  Histochemical analysis showed aberrant expressions of carbohydrate, lipid, and protein in the tissue. Finally, the study reports altered expression status of glucose transporter 1 and hexokinase 2 molecule.  These intermediate molecules are precursors, as well as significant molecules of metabolic pathways which may increase oxidative damage and it can be used as a minimal invasive prognostic indicator of the disease.

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1. Cho, H., Lee, Y. S., Kim, J., Chung, J.-Y., & Kim, J.-H. (2013). Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer. Cancer investigation, 31(9), 607-615.
2. Coleman, R. (2011). Histological and Histochemical Methods, John A. Kiernan. Scion Publishing Ltd., Bloxham, Oxfordshire, UK (2008), www. scionpublishing. com,(Univ. W. Ontario, London, Canada). Urban & Fischer.
3. Eissa, S., & Seada, L. S. (1998). Quantitation of bcl-2 protein in bladder cancer tissue by enzyme immunoassay: comparison with Western blot and immunohistochemistry. Clinical Chemistry, 44(7), 1423-1429.
4. Epstein, J. B., Zhang, L., & Rosin, M. (2002). Advances in the diagnosis of oral premalignant and malignant lesions. Journal-Canadian Dental Association, 68(10), 617-621.
5. Gatenby, R. A., & Gillies, R. J. (2007). Glycolysis in cancer: a potential target for therapy. The international journal of biochemistry & cell biology, 39(7), 1358-1366.
6. Kato, H., Takita, J., Miyazaki, T., Nakajima, M., Fukai, Y., Masuda, N., Tsukada, K. (2002). Glut-1 glucose transporter expression in esophageal squamous cell carcinoma is associated with tumor aggressiveness. Anticancer research, 22(5), 2635-2639.
7. Kunkel, M., Reichert, T. E., Benz, P., Lehr, H. A., Jeong, J. H., Wieand, S., Whiteside, T. L. (2003). Overexpression of Glut‐1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer, 97(4), 1015-1024.
8. Li, S., Yang, X., Wang, P., & Ran, X. (2013). The effects of GLUT1 on the survival of head and neck squamous cell carcinoma. Cellular Physiology and Biochemistry, 32(3), 624-634.
9. Rai, V., Bose, S., Mukherjee, R., Sarbajna, A., & Chakraborty, C. (2018). Evaluation of aberrant metabolism related proteins in oral submucous fibrosis: A pilot study. Journal of Oral Biosciences, 60(4), 87-91.
10. Rai, V., Bose, S., Saha, S., & Chakraborty, C. (2019). Evaluation of oxidative stress and the microenvironment in oral submucous fibrosis. Heliyon, 5(4), e01502.
11. Rai, V., Bose, S., Saha, S., Kumar, V., & Chakraborty, C. (2019). Delineating metabolic dysfunction in cellular metabolism of oral submucous fibrosis using 1H nuclear magnetic resonance spectroscopy. Archives of Oral Biology, 97, 102-108.
12. Rai, V., Mukherjee, R., Ghosh, A. K., Routray, A., & Chakraborty, C. (2017). “Omics” in oral cancer: New approaches for biomarker discovery. Archives of Oral Biology.
13. Rai, V., Mukherjee, R., Routray, A., Ghosh, A. K., Roy, S., Ghosh, B. P., Chakraborty, C. (2018). Serum-based diagnostic prediction of oral submucous fibrosis using FTIR spectrometry. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 189, 322-329.
14. Varela-Centelles, P., López-Cedrún, J., Fernández-Sanromán, J., Seoane-Romero, J., de Melo, N. S., Álvarez-Nóvoa, P., Seoane, J. (2017). Key points and time intervals for early diagnosis in symptomatic oral cancer: a systematic review. International journal of oral and maxillofacial surgery, 46(1), 1-10.
15. Wang, W., Liu, Z., Zhao, L., Sun, J., He, Q., Yan, W., Wang, A. (2017). Hexokinase 2 enhances the metastatic potential of tongue squamous cell carcinoma via the SOD2-H2O2 pathway. Oncotarget, 8(2), 3344.
16. Wolf, A., Agnihotri, S., Micallef, J., Mukherjee, J., Sabha, N., Cairns, R., Guha, A. (2011). Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. Journal of Experimental Medicine, 2(208), 313-326.
17. Higuchi M., Honda T., Proske R.J., Yeh E.T. Regulation of reactive oxygen species-induced apoptosis and necrosis by caspase 3-like proteases. Oncogene. 1998;17:2753–2760.
doi: 10.1038/sj.onc.1202211