DNA methylation of CRB3 is a prognostic biomarker in clear cell renal cell carcinoma
DNA methylation of CRB3 is a prognostic biomarker in clear cell renal cell carcinoma
复制标题
CRB3 的 DNA 甲基化是透明细胞肾细胞癌的预后生物标志物
DOI：
10.1007/s11033-019-04892-7
复制
发表时间：
2019-08-01
影响因子：
2.8
通讯作者：
Liu, Peijun
中科院分区：
文献类型：
--
作者：
Li, Pingping;Liu, Jie;Liu, Peijun
我们先前的研究发现CRB3蛋白在肾透明细胞癌中的表达降低，并且与肾透明细胞癌的TNM分期、病理分级和预后不良有关。本研究旨在探讨CRB3基因甲基化是否降低其表达，从而导致肾细胞癌的进展和预后不良。从肿瘤基因组图谱(TCGA)数据库中提取CRB3DNA甲基化、CRB3mRNA表达和ccRCC临床病理参数的数据。用UALCAN、MethHC、LinkedOmics和Wander软件分析CRB3基因甲基化、CRB3mRNA表达与ccRCC临床病理参数之间的关系。我们发现CRB3在肾细胞癌组织中的表达水平低于正常组织。CcRCC组织中CRB3基因甲基化增加，所有探针均显示CcRCC与正常组织之间存在差异。此外，CRB3DNA甲基化与CRB3mRNA表达呈负相关。CRB3DNA甲基化与肾细胞癌病理分期、T期、N期、M期有关。CRB3DNA甲基化水平较高的肾细胞癌患者总生存期较CRB3DNA甲基化水平较低的肾细胞癌患者短。Cg24798010基因甲基化与肿瘤的偏侧性、病理分期、T分期、M分期、肿瘤组织学分级无N分期、种族有关。此外，用DNA甲基化抑制剂地西他滨处理后，ccRCC细胞中CRB3mRNA的表达上调。提示CRB3基因甲基化可能是肾细胞癌的预后指标和治疗靶点。
Our previous study revealed that CRB3 protein expression was reduced in clear cell renal cell carcinoma (ccRCC) and was associated with TNM stage, pathological grade, and poor prognosis of ccRCC. This study aimed to investigate if DNA methylation of CRB3 decreases its expression, subsequently leading to the progression and poor prognosis of ccRCC. Data for DNA methylation of CRB3, CRB3 mRNA expression, and ccRCC clinicopathological parameters were extracted from the cancer genome atlas (TCGA) database. The relationships among DNA methylation of CRB3, CRB3 mRNA expression, and ccRCC clinicopathological parameters were analyzed using UALCAN, MethHC, LinkedOmics, and Wanderer. We found that CRB3 mRNA levels were lower in ccRCC compared to normal tissues. Methylation of CRB3 increased in ccRCC, with all probes showing differences between ccRCC and normal tissues. Furthermore, CRB3 DNA methylation negatively correlated with CRB3 mRNA expression. CRB3 DNA methylation was also related to pathologic stage, T stage, N stage, and M stage of ccRCC. Overall survival was shorter in ccRCC patients with high CRB3 DNA methylation compared to ccRCC patients with low CRB3 DNA methylation. Methylation of cg24798010, a CRB3 probe, was related to laterality, pathologic stage, T stage, M stage, neoplasm-histologic-grade without N stage, and race. Furthermore, treatment with the DNA methylation inhibitor Decitabine resulted in the upregulation of CRB3 mRNA in ccRCC cell lines. These results indicate that DNA methylation of CRB3 may be both a prognostic marker and therapeutic target for ccRCC.