HMGA2 is associated with epithelial–mesenchymal transition and can predict poor prognosis in nasopharyngeal carcinoma

Abstract

You-You Xia,1,* Li Yin,2,* Hao Tian,1 Wen-Jie Guo,2 Ning Jiang,2 Xue-Song Jiang,2 Jing Wu,1 Meng Chen,1 Jian-Zhong Wu,3 Xia He2 1The Fourth Clinical Medical College of Nanjing Medical University, 2Department of Radiation Oncology, 3Research Center of Clinical Oncology, The Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this paper Objective: High-mobility group protein 2 (HMGA2) and epithelial–mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis. However, the clinical significance of HMGA2 and its relationship with EMT markers in nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the clinicopathological significance and prognostic value of HMGA2, E-cadherin, and vimentin in NPC. Methods: Using immunohistochemistry, HMGA2, E-cadherin, and vimentin expression levels were evaluated in NPC (n=124) and non-tumoral inflammatory nasopharynx (n=20) tissues. The association of HMGA2 and EMT markers with clinicopathological characteristics and relationships between the protein levels and overall survival were analyzed.Results: Compared with non-tumorous tissues, HMGA2 and vimentin levels were markedly increased in NPC tissues, whereas decreased E-cadherin levels were observed (P<0.001). Moreover, HMGA2 expression was positively correlated with vimentin levels (r=0.431, P<0.001) and negatively correlated with E-cadherin amounts (r=−0.413, P<0.001) in NPC tissues. The expression of all three proteins correlated significantly with tumor N stage, TNM stage, and 2-year metastasis. Furthermore, significant correlations were found for T stage, N stage, TNM stage, HMGA2, E-cadherin, and vimentin (all P<0.013) with poor prognosis (univariate analysis). However, multivariate analyses showed that only HMGA2 (hazard ratio [HR]: 2.683, 95% confidence interval [CI]: 1.185–6.077, P=0.018) and N stage (HR: 7.892, 95% CI: 2.731–22.807, P<0.001) were independent predictors of poor prognosis.Conclusion: These results demonstrated that HMGA2, an independent prognostic factor, may promote NPC progression and metastasis, and is significantly associated with EMT proteins. Therefore, HMGA2 may be considered a potential therapeutic target in NPC. Keywords: EMT, NPC, high-mobility group protein 2