Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer

Jingjing Wu, Shizhen Zhang, Jinlan Shan, Zujian Hu, Xiyong Liu, Lirong Chen, Xingchang Ren, Lifang Yao, Hongqiang Sheng, Ling Li, David Ann, Yun Yen, Jian Wang, Xiaochen Wang

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)284-292
Number of pages9
JournalCancer Letters
Volume376
Issue number2
DOIs
Publication statusPublished - Jul 1 2016

Fingerprint

AT-Hook Motifs
Breast Neoplasms
Neoplasms
Biological Phenomena
Transcriptome
DNA Damage
Biomarkers
Phosphorylation
Staining and Labeling

Keywords

  • Breast cancer
  • High mobility group AT-hook 2
  • Prognostic biomarker
  • Tumor progression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer. / Wu, Jingjing; Zhang, Shizhen; Shan, Jinlan; Hu, Zujian; Liu, Xiyong; Chen, Lirong; Ren, Xingchang; Yao, Lifang; Sheng, Hongqiang; Li, Ling; Ann, David; Yen, Yun; Wang, Jian; Wang, Xiaochen.

In: Cancer Letters, Vol. 376, No. 2, 01.07.2016, p. 284-292.

Research output: Contribution to journalArticle

Wu, J, Zhang, S, Shan, J, Hu, Z, Liu, X, Chen, L, Ren, X, Yao, L, Sheng, H, Li, L, Ann, D, Yen, Y, Wang, J & Wang, X 2016, 'Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer', Cancer Letters, vol. 376, no. 2, pp. 284-292. https://doi.org/10.1016/j.canlet.2016.04.005
Wu, Jingjing ; Zhang, Shizhen ; Shan, Jinlan ; Hu, Zujian ; Liu, Xiyong ; Chen, Lirong ; Ren, Xingchang ; Yao, Lifang ; Sheng, Hongqiang ; Li, Ling ; Ann, David ; Yen, Yun ; Wang, Jian ; Wang, Xiaochen. / Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer. In: Cancer Letters. 2016 ; Vol. 376, No. 2. pp. 284-292.
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