1. Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer
- Author
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Ling Li, Jingjing Wu, Jinlan Shan, Zujian Hu, Xingchang Ren, Xiaochen Wang, David K. Ann, Yun Yen, Lifang Yao, Xiyong Liu, Jian Wang, Lirong Chen, Hongqiang Sheng, and Shizhen Zhang
- Subjects
0301 basic medicine ,CA15-3 ,Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Breast Neoplasms ,Kaplan-Meier Estimate ,Transfection ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,HMGA2 ,Cell Movement ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Genetic Predisposition to Disease ,Neoplasm Invasiveness ,Phosphorylation ,Cell Proliferation ,Proportional Hazards Models ,biology ,Gene Expression Profiling ,HMGA2 Protein ,Reproducibility of Results ,Cancer ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Up-Regulation ,Phenotype ,Treatment Outcome ,030104 developmental biology ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer cell ,MCF-7 Cells ,biology.protein ,Biomarker (medicine) ,Female ,Ectopic expression ,Neoplasm Grading ,Tumor Suppressor Protein p53 - Abstract
High mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors. Here, we collected 273 breast cancer (BC) specimens as a training set and 310 specimens as a validation set to examine the expression of HMGA2 by immunohistochemical staining. It was found that HMGA2 expression was significantly positively correlated with advanced tumor grade and poor survival. Subgroup analysis indicated that high level of HMGA2 was significantly correlated with poor prognosis, especially in the subgroups of stage II-III, low pathological grade and non-triple negative breast cancer cases. Gene set enrichment analysis (GSEA) demonstrated a significant positive correlation between HMGA2 level and the gene expression signature of metaplastic and mesenchymal phenotype. Importantly, we also observed that ectopic expression of HMGA2 promoted the migration and invasion of breast cancer cells, and protected cancer cells against genotoxic stress from agents stimulating P53 (Ser15) phosphorylation. As a conclusion, expression of HMGA2 might 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.
- Published
- 2016