Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
Mol Diagn Ther. 2019 Feb;23(1):127-138. doi: 10.1007/s40291-019-00384-3.
Lysophosphatidic acid (LPA) has widely been reported to participate in the numerous biological behaviors of tumors through its receptors. LPA receptor 6 (LPAR6) is a newly identified G protein-coupled receptor of LPA, and few studies have explored the role of LPAR6 in cancer. In breast cancer (BC), LPAR6 has not, as yet, been studied. This study aimed to evaluate LPAR6 expression in BC patients and to explore its possible role in BC.
A total of 98 pairs of clinical BC and para-cancer tissues were collected, and LPAR6 expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier plots were employed for survival analysis. Human BC cell lines were cultured to study decitabine (5-aza-2'-deoxycytidine [5-Aza]) intervention. Bioinformatic analyses were carried out to support the study conclusions and predictions.
LPAR6 expression was significantly reduced in BC tissues (p < 0.001). In the analysis of clinical parameters, LPAR6 expression was related to BC molecular classification (p < 0.05). Furthermore, patients with higher LPAR6 expression had better prognoses (p < 0.001). The CpG islands of LPAR6 were hypermethylated in BC tissues relative to those in para-cancer tissues (p < 0.01). 5-Aza significantly upregulated LPAR6 expression in BC cell lines. Additionally, LPAR6 knockdown significantly promoted cell migration and proliferation in the ZR-75-1 cell line (p < 0.001). Finally, through Gene Set Enrichment Analysis (GSEA), LPAR6 was found to be negatively correlated with cancer-promoting factors and positively correlated with tumor-suppressing factors.
LPAR6 was downregulated in BC, and low LPAR6 expression was related to poor prognosis. The anti-tumor drug 5-Aza significantly upregulated LPAR6 expression in vitro, and LPAR6 might act as a tumor suppressor in BC.
溶血磷脂酸（LPA）通过其受体广泛参与肿瘤的多种生物学行为。LPA 受体 6（LPAR6）是 LPA 的一种新发现的 G 蛋白偶联受体，目前关于 LPAR6 在癌症中的作用的研究较少。在乳腺癌（BC）中，尚未研究 LPAR6。本研究旨在评估 LPAR6 在 BC 患者中的表达，并探讨其在 BC 中的可能作用。
共收集 98 对临床 BC 和癌旁组织，采用实时定量聚合酶链反应（qRT-PCR）评估 LPAR6 表达。采用 Kaplan-Meier 图进行生存分析。培养人 BC 细胞系以研究地西他滨（5-氮杂-2'-脱氧胞苷[5-Aza]）干预。进行生物信息学分析以支持研究结论和预测。
BC 组织中 LPAR6 表达明显降低（p<0.001）。在临床参数分析中，LPAR6 表达与 BC 分子分类相关（p<0.05）。此外，LPAR6 表达较高的患者预后较好（p<0.001）。BC 组织中 LPAR6 的 CpG 岛相对于癌旁组织发生超甲基化（p<0.01）。5-Aza 可显著上调 BC 细胞系中 LPAR6 的表达。此外，LPAR6 敲低显著促进 ZR-75-1 细胞系的细胞迁移和增殖（p<0.001）。最后，通过基因集富集分析（GSEA）发现，LPAR6 与促进癌症的因子呈负相关，与肿瘤抑制因子呈正相关。
LPAR6 在 BC 中下调，低 LPAR6 表达与预后不良相关。抗癌药物 5-Aza 可显著上调体外 LPAR6 的表达，LPAR6 可能在 BC 中起肿瘤抑制作用。
