LGR5 过表达与乳腺癌患者无复发生存不良相关。
LGR5 overexpression confers poor relapse-free survival in breast cancer patients.
机构信息
Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Surgery, Kaohsiung Municipal Hsiao Kang Hospital, Kaohsiung, Taiwan.
出版信息
BMC Cancer. 2018 Feb 22;18(1):219. doi: 10.1186/s12885-018-4018-1.
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.
背景
癌症干细胞（CSCs）被认为通过多种信号通路，包括 Wnt/β-catenin 通路，促进乳腺癌的恶性转化。富含亮氨酸重复序列的 G 蛋白偶联受体 5（LGR5）已被鉴定为与 CSC 相关的 Wnt 调节靶基因，但在乳腺癌背景下其临床意义仍不清楚。因此，本研究旨在探讨 LGR5-β-catenin 轴在乳腺癌中的临床意义。
方法
使用 126 例患者的乳腺癌组织块构建组织微阵列（TMA）。从癌症登记数据库和患者病历中获得组织病理学和临床数据，包括年龄；肿瘤大小；雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体 2（HER2）水平；肿瘤分级；淋巴结（LN）状态；和生存情况。使用半定量免疫组织化学（IHC）染色对 TMA 上的组织进行 LGR5 和 β-catenin 表达评分。我们还通过 ONCOMINE 分析了基于网络的癌症微阵列数据库中可用的 LGR5 表达的细胞数据集。
结果
免疫组织化学染色显示，58 例肿瘤（46%）表现出高 LGR5 表达，而 56 例肿瘤（47%）表现出高 β-catenin 表达。高 LGR5 表达水平与肿瘤大小（p=0.002）、LN 转移状态（p=0.044）和三阴性乳腺癌（p=0.029）显著相关，与我们从 ONCOMINE 数据库中发现的结果一致。此外，我们还发现，β-catenin 表达的乳腺癌与 HER2 过表达呈正相关。最后，就临床结局而言，LGR5-β-catenin 轴高表达的患者与 LGR5-β-catenin 轴低表达的患者相比，无复发生存率（RFS）较差（p=0.027）。
结论
LGR5 过表达与高 T 分期和 LN 转移状态显著相关。高 LGR5 表达还与 RFS 降低相关，表明 LGR5 可能成为乳腺癌患者有前途的预后标志物。
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