Prognostic and Therapeutic Significance of Adhesion-regulating Molecule 1 in Estrogen Receptor-positive Breast Cancer.

INTRODUCTION:Adhesion-regulating molecule 1 (ADRM1) is a polyubiquitin receptor on the 26S proteasome. ADRM1 is upregulated in many cancers. In this study, we evaluated the potential prognostic and predictive value of ADRM1 in breast cancer. MATERIALS AND METHODS:Individual and pooled survival analyses were performed on 19 independent breast cancer microarray datasets. Gene signatures enriched by ADRM1 were also analyzed in pooled datasets. RESULTS:Gene set enrichment analysis revealed that high expression of ADRM1 was significantly associated with aggressive breast cancer. Our findings revealed that ADRM1 mRNA levels were significantly associated with estrogen receptor (ER) status, progesterone receptor status, tumor size, lymph node status, histologic grade, and molecular subtypes. We also found that higher mRNA ADRM1 expression was significantly correlated with poor survival in patients with breast cancer. The prognostic power of ADRM1 mRNA was similar to the 70-gene wound response genes and 21 gene recurrence score; it was superior to TNM staging. The prognostic value of ADRM1 was better in ER-positive (ER⁺) breast cancer cases than in ER-negative breast cancer cases. In cases involving stage II breast cancer, radiotherapy significantly reduced the relative risk of OS in the ADRM1-low subgroup. CONCLUSION:ADRM1 mRNA levels were significantly related to poor outcome in our breast cancer sample population. It could serve as a prognostic biomarker, especially in ER⁺ breast cancer and Luminal A breast cancer cases, as well as a predictive biomarker for ER⁺ breast cancer.

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