Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance.
OBJECTIVE
HMGB1 overexpression has been reported in a variety of human cancers. However, the role of HMGB1 in squamous-cell carcinoma of the head and neck (SCCHN) remains unclear. The aim of the present investigation was to analyse HMGB1 protein expression in both SCCHN tissue and cell levels and to assess its prognostic significance in SCCHN.


METHODS
HMGB1 protein expression in 103 primary SCCHN tissue specimens was analysed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, HMGB1 protein expression was evaluated in cell level by Western blotting.


RESULTS
By Western blotting analysis, all the 5 SCCHN cell lines overexpressed HMGB1 protein, whereas the non-transformed immortalised cell line NP-69 had relatively weak HMGB1 protein expression. Immunohistochemical staining revealed that HMGB1 protein was detected in 91 (91/103, 88.3%) primary tumour samples, but only in 7 (7/16, 43.75%) adjacent non-carcinoma samples (p<0.001); moreover, HMGB1 overexpression was significantly associated with T classification (p=0.001), clinical stage (p<0.001), recurrence (p<0.001) and lymph node metastasis (p<0.001). Survival analysis demonstrated that high HMGB1 expression was significantly associated with shorter disease-free and overall survival (both p<0.001), especially in late patients with SCCHN. When HMGB1 expression and lymph node status were combined, patients with HMGB1 overexpression/lymph node (+) had both poorer disease-free and overall survival than others (both p<0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with SCCHN.


CONCLUSIONS
HMGB1 protein may contribute to the malignant progression of SCCHN, and present as a novel prognostic marker and a potential therapeutic target for patients with SCCHN.
Liu
Yong
Y
Department of Otolaryngology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China.
Xie
Congliang
C
Zhang
Xin
X
Huang
Donghai
D
Zhou
Xiaojuan
X
Tan
Pingqing
P
Qi
Lin
L
Hu
Guoqing
G
Tian
Yongquan
Y
Qiu
Yuanzheng
Y
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured
D024243:HMGB1 Protein; D009363:Neoplasm Proteins