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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2020

01-01-2020 | Breast Cancer | Preclinical study

High mobility group A1 (HMGA1) protein and gene expression correlate with ER-negativity and poor outcomes in breast cancer

Authors: Mikhail Gorbounov, Neil M. Carleton, Rebecca J. Asch-Kendrick, Lingling Xian, Lisa Rooper, Lionel Chia, Ashley Cimino-Mathews, Leslie Cope, Alan Meeker, Vered Stearns, Robert W. Veltri, Young Kyung Bae, Linda M. S. Resar

Published in: Breast Cancer Research and Treatment | Issue 1/2020

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Abstract

Purpose

The high mobility group A1 (HMGA1) chromatin remodeling protein is required for metastatic progression and cancer stem cell properties in preclinical breast cancer models, although its role in breast carcinogenesis has remained unclear. To investigate HMGA1 in primary breast cancer, we evaluated immunoreactivity score (IRS) in tumors from a large cohort of Asian women; HMGA1 gene expression was queried from two independent Western cohorts.

Methods

HMGA1 IRS was generated from breast tumors in Korean women as the product of staining intensity (weak = 1, moderate = 2, strong = 3) and percent positive cells (< 5% = 0, 5–30% = 1, 30–60% = 2, > 60% = 3), and stratified into three groups: low (< 3), intermediate (3–6), high (> 6). We assessed HMGA1 and estrogen receptor (ESR1) gene expression from two large databases (TCGA, METABRIC). Overall survival was ascertained from the METABRIC cohort.

Results

Among 540 primary tumors from Korean women (181 ER-negative, 359 ER-positive), HMGA1 IRS was < 3 in 89 (16.5%), 3–6 in 215 (39.8%), and > 6 in 236 (43.7%). High HMGA1 IRS was associated with estrogen receptor (ER)-negativity (χ2 = 12.07; P = 0.002) and advanced nuclear grade (χ2 = 12.83; P = 0.012). In two large Western cohorts, the HMGA1 gene was overexpressed in breast cancers compared to non-malignant breast tissue (P < 0.0001), including Asian, African American, and Caucasian subgroups. HMGA1 was highest in ER-negative tumors and there was a strong inverse correlation between HMGA1 and ESR1 gene expression (Pearson r = − 0.60, P < 0.0001). Most importantly, high HMGA1 predicted decreased overall survival (P < 0.0001) for all women with breast cancer and further stratified ER-positive tumors into those with inferior outcomes.

Conclusions

Together, our results suggest that HMGA1 contributes to estrogen-independence, tumor progression, and poor outcomes. Moreover, further studies are warranted to determine whether HMGA1 could serve as a prognostic marker and therapeutic target for women with breast cancer.
Appendix
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Metadata
Title
High mobility group A1 (HMGA1) protein and gene expression correlate with ER-negativity and poor outcomes in breast cancer
Authors
Mikhail Gorbounov
Neil M. Carleton
Rebecca J. Asch-Kendrick
Lingling Xian
Lisa Rooper
Lionel Chia
Ashley Cimino-Mathews
Leslie Cope
Alan Meeker
Vered Stearns
Robert W. Veltri
Young Kyung Bae
Linda M. S. Resar
Publication date
01-01-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05419-1

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