UBASH3B promotes tamoxifen resistance and could be negatively regulated by ESR1

Oncotarget
Ketao JinWei Wang

Abstract

To explore the prognostic value of UBASH3B in ER+ breast cancer patients and explore potential molecular mechanisms. Datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were re-analyzed to explore the association between UBASH3B and the progression of ER+ breast cancer. Kaplan-Meier plot analysis with a total of 734 ER+ samples and Gene Set Enrichment Analysis with 632 samples were used in the study. 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....Continue Reading

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Datasets Mentioned

BETA
GSE6532

Methods Mentioned

BETA
ESR
Chip

Software Mentioned

GraphPadPrism5
R
GraphPad
SPSS
GSEA
Gene Set Enrichment Analysis ( GSEA )

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