Evaluation of the Serum Level of High Mobility Group Box 1 Protein in Benign and Malignant Salivary Gland Tumors
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Abstract
Despite a low prevalence, salivary gland tumors (SGTs) represent a diverse set of tumors with a broad range of biological behaviors. Implementation of early detection programs has significantly improved the outcome of treatment and patients' survival. High mobility group box one protein (HMGB1) may likely be a candidate for the detection of SGTs due to its background in other human tumors. This study, for the first time, aimed to investigate the clinical value of HMGB1 in patients with benign and malignant SGTs and analyze its correlation with clinicopathologic outcomes. Using an enzyme-linked immunosorbent assay (ELISA), the serum level of HMGB1 was measured in 85 patients with SGTs (30 benign and 55 malignant cases) and 85 age- and sex-matched healthy individuals. HMGB1 levels had a significant difference between patients with SGTs and healthy controls (2041.4±787.1 pg/ml versus 536.3±374.6 pg/ml, P<0.0001) as well as those with benign and malignant tumors (1680.1±429.7 pg/ml versus 2238.6±867.2 pg/ml, P<0.0001). The serum level of HMGB1 was associated with some clinicopathologic factors, such as the size of the main tumor, clinical stage, and the lymph node metastasis, but not with patients' gender, age as well as the site of the lesions. These results suggest that the serum level of HMGB1 has the potential to be a supportive diagnostic marker for SGTs and can provide a precise assessment of the tumor status. There is no published report regarding the serum level of HMGB1 in SGTs; therefore, further studies are warranted.
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8. Sun S, Zhang W, Cui Z, Chen Q, Xie P, Zhou C, et al. High mobility group box-1 and its clinical value in breast cancer. Onco Targets Ther 2015;8:413-9.
9. Zhang CL, Shu MG, Qi HW, Li LW. Inhibition of tumor angiogenesis by HMGB1 A box peptide. Med Hypotheses 2008;70:343-5.
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11. Shang GH, Jia CQ, Tian H, Xiao W, Li Y, Wang AH, et al. Serum high mobility group box protein 1 as a clinical marker for non-small cell lung cancer. Respir Med 2009;103:1949-53.
12. Martinotti S, Patrone M, Ranzato E. Emerging roles for HMGB1 protein in immunity, inflammation, and cancer. Immunotargets Ther 2015;4:101-9.
13. Biscetti F, Straface G, De Cristofaro R, Lancellotti S, Rizzo P, Arena V, et al. High-mobility group box-1 protein promotes angiogenesis after peripheral ischemia in diabetic mice through a VEGF-dependent mechanism. Diabetes 2010;59:1496-505.
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16. Süren D, Yıldırım M, Demirpençe Ö, Kaya V, Alikanoğlu AS, Bülbüller N, et al. The role of high mobility group box 1 (HMGB1) in colorectal cancer. Med Sci Monit 2014;20:530-7.
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18. Kostova N, Zlateva S, Ugrinova I, Pasheva E. The expression of HMGB1 protein and its receptor RAGE in human malignant tumors. Mol Cell Biochem 2010;337:251-8.
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20. Sasahira T, Kirita T, Oue N, Bhawal UK, Yamamoto K, Fujii K, et al. High mobility group box‐1‐inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma. Cancer Sci 2008;99:1806-12.
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22. Dong YD, Cui L, Peng CH, Cheng DF, Han BS, Huang F. Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncol Rep 2013;29:87-94.
23. Barak V, Meirovitz A, Leibovici V, Rachmut J, Peretz T,
Eliashar R, et al. The diagnostic and prognostic value of tumor markers (CEA, SCC, CYFRA 21-1, TPS) in head and neck cancer patients. Anticancer Res 2015;35:5519-24.
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25. Chung HW, Lee SG, Kim H, Hong DJ, Chung JB, Stroncek D, et al. Serum high mobility group box-1 (HMGB1) is closely associated with the clinical and pathologic features of gastric cancer. J Transl Med 2009;7:38.
26. Buoncervello M, Borghi P, Romagnoli G, Spadaro F, Belardelli F, Toschi E, et al. Apicidin and docetaxel combination treatment drives CTCFL expression and HMGB1 release acting as potential antitumor immune response inducers in metastatic breast cancer cells. Neoplasia 2012;14:855-67.
27. Wang H, Li Z, Sun Y, Xu Z, Han J, Song B, et al. Relationship between high-mobility group box 1 overexpression in ovarian cancer tissue and serum: a meta-analysis. Onco Targets Ther 2015;8:3523-31.
28. Qiu G, Li Y, Liu Z, Wang M, Ge J, Bai X. Clinical value of serum HMGB1 in diagnosis and prognosis of laryngeal squamous cell carcinoma. Med Oncol 2014;31:1-5.
29. Sheng X, Du X, Zhang X, Li D, Lu C, Li Q, et al. Clinical value of serum HMGB1 levels in early detection of recurrent squamous cell carcinoma of uterine cervix: comparison with serum SCCA, CYFRA21-1, and CEA levels. Croat Med J 2009;50:455-64.
30. Wild CA, Brandau S, Lotfi R, Mattheis S, Gu X, Lang S, et al. HMGB1 is overexpressed in tumor cells and promotes activity of regulatory T cells in patients with head and neck cancer. Oral Oncol 2012;48:409-16.
31. Lee H, Song M, Shin N, Shin CH, Min BS, Kim HS, et al. Diagnostic significance of serum HMGB1 in colorectal carcinomas. PLoS One 2012;7:e34318.
32. Cheng BQ, Jia CQ, Liu CT, Lu XF, Zhong N, Zhang ZL, et al. Serum high mobility group box chromosomal protein 1 is associated with clinicopathologic features in patients with hepatocellular carcinoma. Dig Liver Dis 2008;40:446-52.
33. Paek J, Kim YT. The expression of HMGB1 and the receptor for advanced glycation end products (RAGE) in epithelial ovarian cancer. Integr Cancer Sci Ther 2017;4:1-4.
34. Li Y, Tian J, Fu X, Chen Y, Zhang W, Yao H, et al. Serum high mobility group box protein 1 as a clinical marker for ovarian cancer. Neoplasma 2014;61:579-84.
35. Palumbo R, Galvez BG, Pusterla T, De Marchis F, Cossu G, Marcu KB, et al. Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-κB activation. J Cell Biol 2007;179:33-40
36. Sasahira T, Akama Y, Fujii K, Kuniyasu H. Expression of receptor for advanced glycation end products and HMGB1/amphoterin in colorectal adenomas. Virchows Arch 2004;446:411-5
37. Taguchi A, Blood DC, Del Toro G, Canet A, Lee DC, Qu W, et al. Blockade of RAGE–amphoterin signalling suppresses tumour growth and metastases. Nature 2000;405:354-60
38. Maeda S, Hikiba Y, Shibata W, Ohmae T, Yanai A, Ogura K, et al. Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer. Biochem Biophys Res Commun 2007;360:394-400.
2. Rahman B, Mamoon N, Jamal S, Zaib N, Luqman M, Mushtaq S. Malignant tumors of the minor salivary glands in northern Pakistan: a clinicopathological study. Hematol Oncol Stem Cell Ther 2008;1:90-3.
3. Peravali RK, Bhat HHK, Upadya VH, Agarwal A, Naag S. Salivary gland tumors: a diagnostic dilemma! J Maxillofac Oral Surg 2015;14:438-42.
4. Taghavi N, Sargolzaei S, Mashhadiabbas F, Akbarzadeh A, Kardouni P. Salivary gland tumors: a 15-year report from Iran. Turk Patoloji Derg 2016;32:35-9.
5. Jaafari-Ashkavandi Z, Ashraf MJ, Moshaverinia M. Salivary gland tumors: a clinicopathologic study of 366 cases in southern Iran. Asian Pac J Cancer Prev 2013;14:27-30.
6. Shahsavari F, Khaniki M, Farbod M. Prevalence of Salivary Glands Lesions in Iran: A 10-Year Retrospective Study. Oral Surg Oral Med Oral Pathol Oral Radiol 2015;119:e174.
7. Wang X, Luo Y, Li M, Yan H, Sun M, Fan T. Management of salivary gland carcinomas-a review. Oncotarget 2017;8:3946-56.
8. Sun S, Zhang W, Cui Z, Chen Q, Xie P, Zhou C, et al. High mobility group box-1 and its clinical value in breast cancer. Onco Targets Ther 2015;8:413-9.
9. Zhang CL, Shu MG, Qi HW, Li LW. Inhibition of tumor angiogenesis by HMGB1 A box peptide. Med Hypotheses 2008;70:343-5.
10. Mohajertehran F, Ayatollahi H, Khazaeni K, Shakeri MT, Mohtasham N. Overexpression of high-mobility motor box 1 in the blood and tissues of patients with head and neck squamous cell carcinoma. Iran J Otorhinolaryngol 2018;30:261-71.
11. Shang GH, Jia CQ, Tian H, Xiao W, Li Y, Wang AH, et al. Serum high mobility group box protein 1 as a clinical marker for non-small cell lung cancer. Respir Med 2009;103:1949-53.
12. Martinotti S, Patrone M, Ranzato E. Emerging roles for HMGB1 protein in immunity, inflammation, and cancer. Immunotargets Ther 2015;4:101-9.
13. Biscetti F, Straface G, De Cristofaro R, Lancellotti S, Rizzo P, Arena V, et al. High-mobility group box-1 protein promotes angiogenesis after peripheral ischemia in diabetic mice through a VEGF-dependent mechanism. Diabetes 2010;59:1496-505.
14. Li Y, He J, Zhong D, Li J, Liang H. High-mobility group box 1 protein activating nuclear factor-κB to upregulate vascular endothelial growth factor C is involved in lymphangiogenesis and lymphatic node metastasis in colon cancer. J Int Med Res 2015;43:494-505.
15. Tang D, Kang R, Zeh HJ, Lotze MT. High-mobility group box 1 and cancer. Biochim Biophys Acta Gene Regul 2010;1799:131-40.
16. Süren D, Yıldırım M, Demirpençe Ö, Kaya V, Alikanoğlu AS, Bülbüller N, et al. The role of high mobility group box 1 (HMGB1) in colorectal cancer. Med Sci Monit 2014;20:530-7.
17. Bhawal UK, Ozaki Y, Nishimura M, Sugiyama M, Sasahira T, Nomura Y, et al. Association of expression of receptor for advanced glycation end products and invasive activity of oral squamous cell carcinoma. Oncology 2005;69:246-55.
18. Kostova N, Zlateva S, Ugrinova I, Pasheva E. The expression of HMGB1 protein and its receptor RAGE in human malignant tumors. Mol Cell Biochem 2010;337:251-8.
19. Liu Y, Xie C, Zhang X, Huang D, Zhou X, Tan P, et al. Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance. Eur J Cancer 2010;46:3007-15.
20. Sasahira T, Kirita T, Oue N, Bhawal UK, Yamamoto K, Fujii K, et al. High mobility group box‐1‐inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma. Cancer Sci 2008;99:1806-12.
21. Zhao CB, Bao JM, Lu YJ, Zhao T, Zhou XH, Zheng DY, et al. Co-expression of RAGE and HMGB1 is associated with cancer progression and poor patient outcome of prostate cancer. Am J Cancer Res 2014;4:369-377.
22. Dong YD, Cui L, Peng CH, Cheng DF, Han BS, Huang F. Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncol Rep 2013;29:87-94.
23. Barak V, Meirovitz A, Leibovici V, Rachmut J, Peretz T,
Eliashar R, et al. The diagnostic and prognostic value of tumor markers (CEA, SCC, CYFRA 21-1, TPS) in head and neck cancer patients. Anticancer Res 2015;35:5519-24.
24. Yuan C, Yang K, Tang H, Chen D. Diagnostic values of serum tumor markers Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP in oral/oropharyngeal squamous cell carcinoma. Onco Targets Ther 2016;9:3381-6.
25. Chung HW, Lee SG, Kim H, Hong DJ, Chung JB, Stroncek D, et al. Serum high mobility group box-1 (HMGB1) is closely associated with the clinical and pathologic features of gastric cancer. J Transl Med 2009;7:38.
26. Buoncervello M, Borghi P, Romagnoli G, Spadaro F, Belardelli F, Toschi E, et al. Apicidin and docetaxel combination treatment drives CTCFL expression and HMGB1 release acting as potential antitumor immune response inducers in metastatic breast cancer cells. Neoplasia 2012;14:855-67.
27. Wang H, Li Z, Sun Y, Xu Z, Han J, Song B, et al. Relationship between high-mobility group box 1 overexpression in ovarian cancer tissue and serum: a meta-analysis. Onco Targets Ther 2015;8:3523-31.
28. Qiu G, Li Y, Liu Z, Wang M, Ge J, Bai X. Clinical value of serum HMGB1 in diagnosis and prognosis of laryngeal squamous cell carcinoma. Med Oncol 2014;31:1-5.
29. Sheng X, Du X, Zhang X, Li D, Lu C, Li Q, et al. Clinical value of serum HMGB1 levels in early detection of recurrent squamous cell carcinoma of uterine cervix: comparison with serum SCCA, CYFRA21-1, and CEA levels. Croat Med J 2009;50:455-64.
30. Wild CA, Brandau S, Lotfi R, Mattheis S, Gu X, Lang S, et al. HMGB1 is overexpressed in tumor cells and promotes activity of regulatory T cells in patients with head and neck cancer. Oral Oncol 2012;48:409-16.
31. Lee H, Song M, Shin N, Shin CH, Min BS, Kim HS, et al. Diagnostic significance of serum HMGB1 in colorectal carcinomas. PLoS One 2012;7:e34318.
32. Cheng BQ, Jia CQ, Liu CT, Lu XF, Zhong N, Zhang ZL, et al. Serum high mobility group box chromosomal protein 1 is associated with clinicopathologic features in patients with hepatocellular carcinoma. Dig Liver Dis 2008;40:446-52.
33. Paek J, Kim YT. The expression of HMGB1 and the receptor for advanced glycation end products (RAGE) in epithelial ovarian cancer. Integr Cancer Sci Ther 2017;4:1-4.
34. Li Y, Tian J, Fu X, Chen Y, Zhang W, Yao H, et al. Serum high mobility group box protein 1 as a clinical marker for ovarian cancer. Neoplasma 2014;61:579-84.
35. Palumbo R, Galvez BG, Pusterla T, De Marchis F, Cossu G, Marcu KB, et al. Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-κB activation. J Cell Biol 2007;179:33-40
36. Sasahira T, Akama Y, Fujii K, Kuniyasu H. Expression of receptor for advanced glycation end products and HMGB1/amphoterin in colorectal adenomas. Virchows Arch 2004;446:411-5
37. Taguchi A, Blood DC, Del Toro G, Canet A, Lee DC, Qu W, et al. Blockade of RAGE–amphoterin signalling suppresses tumour growth and metastases. Nature 2000;405:354-60
38. Maeda S, Hikiba Y, Shibata W, Ohmae T, Yanai A, Ogura K, et al. Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer. Biochem Biophys Res Commun 2007;360:394-400.
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| Issue | Vol 59, No 9 (2021) | |
| Section | Articles | |
| DOI | https://doi.org/10.18502/acta.v59i9.7553 | |
| Keywords | ||
| Salivary gland tumors High mobility group box one protein (HMGB1) Clinicopathologic factors | ||
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How to Cite
1.
Mardani M, Andisheh-Tadbir A, Pourshahian S, Khademi B, Malekzadeh M. Evaluation of the Serum Level of High Mobility Group Box 1 Protein in Benign and Malignant Salivary Gland Tumors. Acta Med Iran. 2021;59(9):530-535.
