Overexpression of HMGA2 as a prognostic indicator in breast cancer.

10091 Background: As a non-histone chromosomal protein, high mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes, and is upregulated in a variety of tumors. However, no detailed studies have examined the association between HMGA2 protein level and the prognosis of breast cancer (BC) patients. Here, we aimed to explore whether the levels of HMGA2 could predict prognosis for BC patients. Methods: We collected 273 BC specimens from the Second Affiliated Hospital of Zhejiang University (ZJU) as a training set. 310 specimens from the National Engineering Center for Biochip at Shanghai (SBC) were served as a validatory set to examine the expression of HMGA2 by immunohistochemical stainings. The Kaplan–Meier analysis and COX proportional hazard model were employed to analyze the survival rate. Results: We found that HMGA2 expression was significantly positive correlated with advanced tumor grade (p< 0.05) and poor survival of BC patients. The adjusted HRs for overall survival were 4.24, (95% CI: 1.17-15.37) and 2.06, (95% CI: 1.21-3.49) in training and validation sets, respectively. Subgroup analysis indicated that high level of HMGA2 was significantly correlated to poor prognosis, especially in the subgroups of advanced clinical stage (HR: 2.06, 95% CI: 1.14-3.72), low pathological grade (HR: 7.28, 95% CI: 1.57-33.83) and non-triple negative breast cancer cases (HR: 2.19, 95% CI: 1.22-3.91). Gene set enrichment analysis (GSEA) demonstrated a significant positive correlation between HMGA2 level and the gene expression signature of metaplastic and mesenchymal phenotype (p< 0.05). Conclusions: Expression of HMGA2 may indicate more advanced malignancy of breast cancer. Thus we believe HMGA2 could serve as a biomarker of poor prognosis and a novel target in treating BC tumors.