Department of Endocrinology, Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, P.R. China.
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, P.R. China.
BMC Cancer. 2022 Sep 5;22(1):951. doi: 10.1186/s12885-022-10038-z.
Breast cancer is the most common female tumors arising worldwide, and genetic and epigenetic events are constantly accumulated in breast tumorigenesis. The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel, mainly maintaining Zn, Ca and Mg homeostasis. It is also involved in regulating proliferation and migration in various cancers including breast cancer. However, epigenetic alterations (such as promoter methylation) of TRPM7 and their correlation with clinical outcomes in breast cancer patients remain largely unclear. In this study, we found that TRPM7 was highly expressed in the luminal A subtype of breast cancers but no other subtypes compared with GTEx (Genotype-Tissue Expression Rad) or normal samples by analyzing the TCGA database. Correspondingly, TRPM7 was methylated in 42.7% (93 of 219) of breast cancers. Further studies found that promoter methylation of TRPM7 were significantly associated with better clinical outcomes in breast cancer patients, especially in the Luminal A subtype. Besides, methylated TRPM7 was correlated with less number of metastatic lymph nodes and longer local failure free survival time in this subtype. In summary, our data indicate that promoter methylation of TRPM7 may predict poor prognosis in patients with luminal A breast cancer.
乳腺癌是全球范围内最常见的女性肿瘤,遗传和表观遗传事件在乳腺癌的发生过程中不断积累。黑色素瘤相关的瞬时受体电位 7 通道(TRPM7)是一种非选择性阳离子通道,主要维持 Zn、Ca 和 Mg 的体内平衡。它还参与调节包括乳腺癌在内的各种癌症的增殖和迁移。然而,TRPM7 的表观遗传改变(如启动子甲基化)及其与乳腺癌患者临床结局的相关性在很大程度上仍不清楚。在这项研究中,我们通过分析 TCGA 数据库发现,与 GTEx(基因型组织表达 Rad)或正常样本相比,TRPM7 在乳腺癌的腔 A 亚型中高表达,但在其他亚型中没有表达。相应地,TRPM7 在 42.7%(93/219)的乳腺癌中发生甲基化。进一步的研究发现,TRPM7 启动子甲基化与乳腺癌患者的临床结局显著相关,尤其是在腔 A 亚型中。此外,在该亚型中,甲基化的 TRPM7 与较少的转移性淋巴结数量和更长的局部无失败生存时间相关。总之,我们的数据表明,TRPM7 启动子甲基化可能预测腔 A 型乳腺癌患者的不良预后。