Increased expression of high-mobility group A2: A novel independent indicator of poor prognosis in patients with esophageal squamous cell carcinoma

J Cancer Res Ther. 2016 Oct-Dec;12(4):1291-1297. doi: 10.4103/0973-1482.180616.

Abstract

Purpose: Although high-mobility group A2 (HMGA2) protein has been reported to participate in cancer progression and metastasis, its clinical relationship with tumor invasion, lymph node metastasis, and prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to analyze the clinical and prognostic significance of HMGA2 in ESCC patients after curative resection.

Materials and methods: The expression of HMGA2 protein was evaluated by using immunohistochemistry in a tissue microarray (TMA) containing ESCC lesions and adjacent normal esophageal epithelial tissues from 96 patients who had undergone curative resection. TMA was constructed by Shanghai Biochip Co. Ltd., Shanghai, China. The relationship between HMGA2 expression and clinicopathological parameters and prognosis was further analyzed.

Results: HMGA2 expression was significantly higher in ESCC tissues compared with that of the adjacent noncancerous tissues (P < 0.001). High expression of HMGA2 was significantly related to tumor size, lymph node metastasis, and advanced tumor-node-metastasis stage (P < 0.05). Patients with low expression of HMGA2 had a better prognosis than those with high expression (χ2 = 5.069, P = 0.024). Univariate analysis showed that age (P = 0.041), depth of tumor invasion (P = 0.031), lymph node status (P = 0.001), and HMGA2 expression (P = 0.024) were correlated with prognosis. Multivariate analysis showed that HMGA2 expression (hazard ratio [HR]: 0.539; 95% confidence interval [95% CI]: 0.302-0.963, P = 0.037) and lymph node metastasis (HR: 0.504; 95% CI: 0.310-0.820, P = 0.006) were independent prognostic factors for overall survival.

Conclusions: High HMGA2 expression was related to lymph node metastasis and poor prognosis in ESCC. Our results indicated that HMGA2 could act as a potential biomarker for prognosis evaluation of ESCC patients.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression
  • HMGA2 Protein / genetics
  • HMGA2 Protein / metabolism*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Tissue Array Analysis
  • Tumor Burden

Substances

  • HMGA2 Protein