Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinoma
Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinoma
复制标题
ELMO1 的综合分析，作为肝细胞癌肿瘤突变负荷和上皮间质转化之间的联系
DOI：
10.1016/j.ebiom.2019.07.002
复制
发表时间：
2019-08-01
期刊：
影响因子：
11.1
通讯作者：
Shen, Shunli
中科院分区：
文献类型：
--
作者：
Peng, Hong;Zhang, Yi;Shen, Shunli
背景：上皮间质转化（EMT）是肿瘤细胞转移的关键。最近，据报道，EMT与炎性肿瘤微环境相关，因此可能是免疫检查点阻断剂的预测生物标志物。然而，其潜在的机制尚不清楚。方法：我们的HCC队列，TCGA和GEO数据集的患者生存数据通过Kaplan-Meier分析确定。ELMO 1在HCC中的功能作用通过一系列体外和体内实验来证明。基因芯片分析用于证明ELMO 1的潜在机制。从TCGA数据集检索的数据被用来确定ELMO 1，EMT和TMB.Findings的关系：在这里，我们报告了一个不可或缺的作用ELMO 1在EMT与肿瘤突变负担（TMB）。其是免疫检查点阻断剂应答的有希望的生物标志物。ELMO 1表达上调与肝细胞癌（HCC）的不良预后以及体外和体内细胞生长、侵袭、迁移、血管生成和EMT增加相关。从机制上讲，我们提供了ELMO 1通过PI 3 K/Akt信号转导调节SOX 10表达并诱导EMT的证据。而且。ELMO 1与TMB呈负相关，表明EMT和TMB之间存在负相关关系。解释：ELMO 1作为EMT和TMB之间的联系，为ELMO 1作为HCC治疗靶点的进一步发展提供了机制基础，并可能成为免疫检查点阻断剂反应的有希望的生物标志物。
Background: Epithelial-mesenchymal transition (EMT) is critical for cancer cell metastasis. Recently, EMT was reported to be associated with the inflammatory tumour microenvironment and, therefore, might be a predictive biomarker for immune checkpoint blockade agents. However, the underlying mechanism is still unclear.Methods: Patient survival data for our HCC cohort, TCGA and GEO datasets were determined by Kaplan-Meier analysis. The functional roles of ELMO1 in HCC were demonstrated by a series of in vitro and in vivo experiments. Gene microarray analysis was used to demonstrate potential mechanisms of ELMO1. Data retrieved from the TCGA datasets were used to determine the relationships of ELMO1, EMT and TMB.Findings: Here, we report an indispensable role for ELMO1 in linking EMT with tumour mutation burden (TMB). which is a promising biomarker for the immune checkpoint blockade agent response. Upregulated ELMO1 expression is associated with a poor prognosis in hepatocellular carcinoma (HCC), as well as increased cell growth, invasion, migration, angiogenesis and EMT in vitro and in vivo. Mechanistically, we provide evidence that ELMO1 regulates SOX10 expression and induces EMT through PI3K/Akt signalling. Moreover. ELMO1 is negatively assodated with TMB, indicating a negative relationship between EMT and TMB.Interpretation: ELMO1 serves as a link between EMT and TMB, providing a mechanistic basis for the further development of ELMO1 as a therapeutic target against HCC and potentially a promising biomarker of the immune checkpoint blockade agent response.