title: Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer.
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.
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Shizhen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Shan
authors.affiliation: Department of Breast Surgery, Hangzhou Traditional Chinese Medical Hospital, Hangzhou, Zhejiang, China.
authors.forename: Zujian
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Biomarker Development, California Cancer Institute, Sino-America Cancer Foundation, Temple City, CA, USA.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Lirong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathology, Hangzhou Traditional Chinese Medical Hospital, Hangzhou, Zhejiang, China.
authors.forename: Xingchang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Diabetes and Metabolic Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ann
authors.affiliation: PhD Program of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Electronic address: yyen@tmu.edu.tw.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.affiliation: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: wangjian519@zju.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: wangxiaochen@zju.edu.cn.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010766:Phosphorylation; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012307:Risk Factors; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D025743:HMGA2 Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Breast cancer; High mobility group AT-hook 2; Prognostic biomarker; Tumor progression