UBASH3B promotes tamoxifen resistance and could be negatively regulated by ESR1

Ketao Jin; Huanrong Lan; Junyu Zhang; Jieqing Lv; Yuan Chen; Kang Yu; Wei Wang

doi:10.18632/oncotarget.23608

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Research Papers:

UBASH3B promotes tamoxifen resistance and could be negatively regulated by ESR1

Ketao Jin, Huanrong Lan, Junyu Zhang, Jieqing Lv, Yuan Chen, Kang Yu and Wei Wang _

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Oncotarget. 2018; 9:8326-8333. https://doi.org/10.18632/oncotarget.23608

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Abstract

Ketao Jin1,*, Huanrong Lan2,*, Junyu Zhang3, Jieqing Lv1, Yuan Chen4, Kang Yu5 and Wei Wang4

1Department of Colorectal Surgery, Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, 312000, Zhejiang Province, P.R. China

2Department of Breast and Thyroid Surgery, Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, 312000, Zhejiang Province, P.R. China

3Department of Hematology, The Fifth Affiliated Hospital of Wenzhou Medical School, Lishui, 323000, Zhejiang Province, P.R. China

4Department of Pathology, Zhejiang Provincial People’s Hospital, Hangzhou, 310014, Zhejiang Province, P.R. China

5Department of Hematology, The First Affiliated Hospital of Wenzhou Medical School, Wenzhou, 323000, Zhejiang Province, P.R. China

*These authors contributed equally to this work

Correspondence to:

Wei Wang, email: [email protected]

Kang Yu, email: [email protected]

Keywords: UBASH3B; breast cancer; tamoxifen resistance; TP53 mutation; prognosis

Received: May 30, 2017 Accepted: November 08, 2017 Published: December 22, 2017

ABSTRACT

Purpose: To explore the prognostic value of UBASH3B in ER+ breast cancer patients and explore potential molecular mechanisms.

Results: High expression of UBASH3B is negatively correlated with distant metastasis free survival (DMFS, P = 0.01, P = 0.045, P = 0.04 in 2 independent datasets and a merged dataset, respectively), disease specific survival (DSS, P = 0.028) and disease free survival (DFS, P = 0.0052, P = 0.011, P = 0.016 in 3 independent datasets, respectively) in ER+ breast cancer patients. Subset analysis found that UBASH3B also has prognostic value on both lymph node positive and negative sub-populations with ER+ breast cancer. This study also demonstrates that UBASH3B expression is tightly associated with tamoxifen resistance and TP53 mutation, which explains the association between UBASH3B and poor prognosis of ER+ breast cancer. Further analyses show that the expression of UBASH3B is affected by promoter methylation and copy number loss. Besides, UBASH3B is inversely correlated with ER and down-regulated by ER. Importantly, we find cisplatin could be a therapeutic option targeting on UBASH3B in clinical settings.

Conclusions: UBASH3B is negatively regulated by ER and confers poor outcome in ER+ breast cancer patients. Cisplatin is a potential therapeutic option for the management of breast cancer patients with high expression of UBASH3B.

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Research Papers:

UBASH3B promotes tamoxifen resistance and could be negatively regulated by ESR1

Abstract