LGR5 overexpression confers poor relapse-free survival in breast cancer patients.
BACKGROUND
Cancer stem cells (CSCs) are believed to promote the malignant transformation of breast cancer via multiple signaling pathways, including the Wnt/β-catenin pathway. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has been identified as a CSC-associated Wnt-regulated target gene, but its clinical significance in the context of breast cancer remains elusive. Therefore, the purpose of this study was to investigate the clinical significance of the LGR5-β-catenin axis in breast cancer.


METHODS
Breast cancer tissue blocks from 126 patients were used to construct a tissue microarray (TMA). Histopathological and clinical data including age; tumor size; estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) level; tumor grade; lymph node (LN) status; and survival were obtained from the cancer registry database and patients' medical records. Tissue on the breast TMA was scored for LGR5 and β-catenin expression using semi-quantitative immunohistochemical (IHC) staining. We also analyzed LGR5 expression in cellular datasets available through ONCOMINE, a web-based cancer microarray database.


RESULTS
Immunohistochemical staining revealed that 58 tumors (46%) exhibited high LGR5 expression, whereas 56 tumors (47%) displayed high β-catenin expression. High levels of LGR5 expression were significantly associated with tumor size (p = 0.002), LN metastasis status (p = 0.044), and triple-negative breast cancer (p = 0.029), consistent with our findings from the ONCOMINE database. In addition, we also found that β-catenin -expressing breast cancers were positive correlated with HER2 overexpression. Finally, with respect to clinical outcomes, patients with high levels of LGR5-β-catenin axis expression exhibited poorer relapse-free survival (RFS) compared to patients with low levels of LGR5-β-catenin axis expression (p = 0.027).


CONCLUSION
LGR5 overexpression was significantly associated with high T stage and LN metastasis status. High LGR5 expression was also associated with reduced RFS, indicating that LGR5 may represent a promising prognostic marker for breast cancer patients.
['Hou|Ming-Feng|MF|', 'Chen|Po-Ming|PM|', 'Chu|Pei-Yi|PY|']
D000328:Adult D000368:Aged D001943:Breast Neoplasms D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008207:Lymphatic Metastasis D008875:Middle Aged D009364:Neoplasm Recurrence, Local D014411:Neoplastic Stem Cells D011379:Prognosis D018719:Receptor, ErbB-2 D043562:Receptors, G-Protein-Coupled D015854:Up-Regulation D060449:Wnt Signaling Pathway D051176:beta Catenin
LGR5 Breast cancer Cancer stem cell