Clinical Value of High Mobility Group Box 1 and the Receptor for Advanced Glycation Endproducts in Head and Neck Cancer: A Systematic Review

Nguyen, Austin; Bhavsar, Sheila; Riley, Erinn; Caponetti, Gabriel; Agrawal, Devendra

doi:10.1055/s-0036-1583168

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International Archives of Otorhinolaryngology

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Sumário

Systematic Review • Int. Arch. Otorhinolaryngol. 20 (04) • Oct-Dec 2016 • https://doi.org/10.1055/s-0036-1583168 copy

Clinical Value of High Mobility Group Box 1 and the Receptor for Advanced Glycation Endproducts in Head and Neck Cancer: A Systematic Review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction

High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers.

Objectives

To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas.

Data synthesis

A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity.

Conclusion

High mobility group box 1 and the receptor for advanced glycation endproducts are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.

Keywords:
HMGB1 protein; advanced; glycosylation end product-specific receptor; head and neck neoplasms

Study	Malignancy	Sample type	N (total)	N (cancer)	Age, mean/median (range)	Sex, M:F	Patient notes
Sasahira et al ³¹31 Sasahira T, Kirita T, Bhawal UK, et al. The expression of receptor for advanced glycation end products is associated with angiogenesis in human oral squamous cell carcinoma. Virchows Arch 2007; 450(3):287-295	OSCC	FFPE tissue	20	20	69.1 (41–83)	10:10	−
Sasahira et al ³⁵35 Sasahira T, Kirita T, Oue N, et al. High mobility group box-1inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma. Cancer Sci 2008;99(9):1806-1812	OSCC	FFPE tissue	62	62	−	35:27	Treatment naive
Wu et al ³⁶36 Wu D, Ding Y, Wang S, Zhang Q, Liu L. Increased expression of high mobility group box 1 (HMGB1) is associated with progression and poor prognosis in human nasopharyngeal carcinoma. J Pathol 2008;216(2):167-175	NPC	FFPE tissue	166	166	47.7 (13–74)	133:33	Treatment naive
Landesberg et al ³²32 Landesberg R, Woo V, Huang L, et al. The expression of the receptor for glycation endproducts (RAGE) in oral squamous cell carcinomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 105(5):617-624	OSCC	FFPE tissue	50	38	A: 69 (28–92).B: 72 (51–88).C: 66 (55–88).	A: 4:7.B: 7:7.C: 6:2*	A: Well-differentiated tumorB: Moderately-differentiated tumorC: Poorly-differentiated tumor
Tsuji et al ³³33 Tsuji A, Wakisaka N, Kondo S, Murono S, Furukawa M, Yoshizaki T. Induction of receptor for advanced glycation end products by EBV latent membrane protein 1 and its correlation with angiogenesis and cervical lymph node metastasis in nasopharyngeal carcinoma. Clin Cancer Res 2008;14(17):5368-5375	NPC	FFPE tissue	42	42	−	−	−
Liu et al ³⁷37 Liu Y, Xie C, Zhang X, et al. Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance. Eur J Cancer 2010;46(16):3007-3015	HNSCC	FFPE tissue	103	103	57.86 (27–80)	99:4	−
Wild et al ³⁸38 Wild CA, Brandau S, Lotfi R, 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(5):409-416	HNSCC	Serum and frozen tissue	52	35	64 ± 10*	29:6*	Treatment naive
Qiu et al ³⁹39 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(12):316	LSCC	Serum	121	71	54.5 ± 14.0*	54:17*	Treatment naive
Hanakawa et al ⁴⁰40 Hanakawa H, Orita Y, Sato Y, et al. Does HMGB1 predict occult neck lymph node metastasis in early tongue carcinoma? A case-control study of 26 patients. J Laryngol Otol 2014;128(10):926-931	Tongue SCC	FFPE tissue	26	26	69 (29–87)	15:11	Treatment naive
Supic et al ⁴¹41 Supic G, Kozomara R, Zeljic K, et al. HMGB1 genetic polymorphisms in oral squamous cell carcinoma and oral lichen planus patients. Oral Dis 2015;21(4):536-543	OSCC	Tumor tissue (unspecified) or blood (controls)	246	93	58 (36–80)*	69:24*	All received primary surgery followed by radiotherapy. 24 received neoadjuvant cisplatin/5-fluorouracil chemotherapy.
Su et al ³⁴34 Su S, Chien M, Lin C, Chen M, Yang S. RAGE gene polymorphism and environmental factor in the risk of oral cancer. J Dent Res 2015 ; 94(3):403-411	OSCC	Blood	1210	618	54.29 ± 11.28*	596:22*	−

Study	HMGB1 or RAGE	Assay	Clinic pathological characteristics or prognosis
Sasahira et al ³¹31 Sasahira T, Kirita T, Bhawal UK, et al. The expression of receptor for advanced glycation end products is associated with angiogenesis in human oral squamous cell carcinoma. Virchows Arch 2007; 450(3):287-295	RAGE (OSCC)	IHC and ELISA	• Lower in T1-T2 stages than T3-T4 (p= 0.0408).• Correlated with MVD (p= 0.0123) and VEGF expression (p= 0.0344).• No correlation with N stage, age, sex, histological differentiation, LVD.
Sasahira et al ³⁵35 Sasahira T, Kirita T, Oue N, et al. High mobility group box-1inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma. Cancer Sci 2008;99(9):1806-1812	HMGB1 (OSCC)	IHC	• High expression in cancer cell nuclei and nodal metastatic foci.• Correlated with VEGF-C and VEGF-D expression (p< 0.001)
Wu et al ³⁶36 Wu D, Ding Y, Wang S, Zhang Q, Liu L. Increased expression of high mobility group box 1 (HMGB1) is associated with progression and poor prognosis in human nasopharyngeal carcinoma. J Pathol 2008;216(2):167-175	HMGB1 (NPC)	IHC	• Detected in 53.6% of cases, higher in malignant tissue.• Correlated with T classification (p= 0.01), N classification (p= 0.003), distant metastasis (p= 0.046), clinical stage (p< 0.001), initial radiotherapy response (p= 0.034), overall survival (p< 0.001), and disease-free survival (p< 0.001).
Landesberg et al ³²32 Landesberg R, Woo V, Huang L, et al. The expression of the receptor for glycation endproducts (RAGE) in oral squamous cell carcinomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 105(5):617-624	RAGE (OSCC)	IHC and Western blot	• Expression was significantly different by tumor differentiation (p< 0.05): 100% of well-differentiated, 75% of well-to-moderately differentiated, 14% of moderate-to-poorly differentiated, 0% of poorly differentiated.• RAGE was highest in normal tissue and trended toward decreased levels with less tumor differentiation.
Tsuji et al ³³33 Tsuji A, Wakisaka N, Kondo S, Murono S, Furukawa M, Yoshizaki T. Induction of receptor for advanced glycation end products by EBV latent membrane protein 1 and its correlation with angiogenesis and cervical lymph node metastasis in nasopharyngeal carcinoma. Clin Cancer Res 2008;14(17):5368-5375	RAGE (NPC)	IHC	• Tumor expression correlated with MVD (p= 0.0049), suggestive of the important role of RAGE in angiogenesis.• Expression was higher with lymph node metastasis (p= 0.0005).
Liu et al ³⁷37 Liu Y, Xie C, Zhang X, et al. Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance. Eur J Cancer 2010;46(16):3007-3015	HMGB1 (HNSCC)	IHC	• Expressed in 88.3% of primary tumor samples and 43.7% in adjacent normal tissue (p< 0.001).• Correlated with tumor T classification (p= 0.001), advanced stage (p< 0.001), lymph node metastasis (p< 0.001) recurrence (p< 0.001), disease-free survival (p< 0.001), and overall survival (p< 0.001).• Was not correlated with age, alcohol intake, smoking, tumor grade, and tumor site.
Wild et al ³⁸38 Wild CA, Brandau S, Lotfi R, 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(5):409-416	HMGB1 (HNSCC)	IF, real-time PCR, and ELISA	• Expressed more strongly in tumor tissue than tumor-adjacent stroma (p= 0.005).• HMGB1 levels were higher in sera of HNSCC patients than controls (p= 0.002).
Qiu et al ³⁹39 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(12):316	HMGB1 (LSCC)	ELISA	• Associated with T classification (p= 0.005), N classification (p= 0.002), and clinical stage (p= 0.001).• High HMGB1 (cutoff 4.80 ng/mL) was associated with poorer overall survival rate (p= 0.036).• Diagnosis of LSCC: 42.0% sensitive, 88.3% specific, positive predictive value of 52.9% (cutoff 4.80 ng/mL)
Hanakawa et al ⁴⁰40 Hanakawa H, Orita Y, Sato Y, et al. Does HMGB1 predict occult neck lymph node metastasis in early tongue carcinoma? A case-control study of 26 patients. J Laryngol Otol 2014;128(10):926-931	HMGB1 (Tongue SCC)	IHC	• Expression is not significantly associated with late neck metastases.
Supic et al ⁴¹41 Supic G, Kozomara R, Zeljic K, et al. HMGB1 genetic polymorphisms in oral squamous cell carcinoma and oral lichen planus patients. Oral Dis 2015;21(4):536-543	HMGB1 (OSCC)	TaqMan genotyping	HMGB1 G/C polymorphism analysis:• 1177GG genotype had higher prevalence of advance tumor stage III (p= 0.016) and significantly lower RFS (p= 0.000).• 3814CC genotype had higher prevalence of nodal metastasis and advance tumor stage III (p= 0.019).
Su et al ³⁴34 Su S, Chien M, Lin C, Chen M, Yang S. RAGE gene polymorphism and environmental factor in the risk of oral cancer. J Dent Res 2015 ; 94(3):403-411	RAGE (OSCC)	TaqMan genotyping	• -429TC genotype was associated with oral cancer incidence (OR, 1.870; 95% CI, 1.323–2.644) and late stage tumors (OR, 1.644; 95% CI, 1.083 to 2.493).

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[1] Address for correspondence Devendra Agrawal, PhD, Department of Clinical and Translational Science, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68172, United States (e-mail: DevendraAgrawal@creighton.edu).