EP300 as an oncogene correlates with poor prognosis in esophageal squamous carcinoma
EP300 as an oncogene correlates with poor prognosis in esophageal squamous carcinoma
复制标题
EP300作为癌基因与食管鳞癌的不良预后相关
DOI：
10.7150/jca.34261
复制
发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Cheng, Xiaolong
中科院分区：
文献类型：
--
作者：
Bi, Yanghui;Kong, Pengzhou;Cheng, Xiaolong
E1 A结合蛋白P300（EP 300）是食管鳞癌中组蛋白修饰相关基因的突变之一。然而，其临床意义，潜在的功能和机制仍然难以捉摸。研究方法：对325例食管鳞状细胞癌（ESCC）患者的基因组测序数据进行整合，筛选出一系列频繁突变的组蛋白修饰基因。选取EP 300作为研究对象，分析其临床意义和功能，并进行RNA测序，探讨其可能的作用机制。结果如下：在35个组蛋白修饰基因中，EP 300基因在食管鳞癌中不仅是一个显著突变的基因，而且是一个突变频率超过10%的基因。EP 300基因突变与肿瘤分级、病理T分期及淋巴结转移有关，提示其累积生存期较短。免疫组化分析显示EP 300在ESCC肿瘤组织中的表达明显增高，其表达水平与ESCC患者的生存率相关。此外，我们发现，EP 300敲低导致抑制细胞增殖，集落形成，迁移和侵袭。RNA测序结果显示，EP 300基因敲低导致与血管生成、缺氧和上皮-间质转化（EMT）相关的基因表达显著改变。结论：总之，我们的研究确定了ESCC中EP 300的新作用和机制，并为ESCC的治疗提供了表观遗传学治疗策略。
E1A Binding Protein P300 (EP300) is one of the mutations of genes involved in histone modifications in esophageal squamous cell carcinoma (ESCC). However, its clinical relevance, potential function and mechanisms have remained elusive. Methods: Genomic sequencing datas from 325 esophageal squamous cell carcinoma (ESCC) cases were integrated and screened a series of frequently mutated histone modifier genes. EP300 was selected to further analyze its clinical significance, function and RNA-sequencing was performed to explore its potential mechanism. Results: Of 35 histone modifier genes, EP300 was not only a significantly mutated gene but also a frequently mutated gene with a mutation frequency of more than 10% in ESCC. EP300 mutation was associated with tumor grade, pathological T stage and lymph node metastasis, predicting a shorter cumulative survival status. Immunohistochemical analysis showed that EP300 expression was significantly higher in ESCC tumor tissues, and the expression levels were associated with poor survival of ESCC patients. Moreover, we found that EP300 knockdown led to inhibition of cell proliferation, colony formation, migration and invasion. RNA-sequencing showed EP300 knockdown led to a significant change of genes expression associated with angiogenesis, hypoxia and epithelial-to-mesenchymal transition (EMT). Conclusions: Taken together, our study identified a novel role and mechanism of EP300 in ESCC and provided epigenetic therapeutic strategies for the treatment of ESCC.