Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinomaResearch in context
Hong Peng,
Yi Zhang,
Zhiwei Zhou,
Yu Guo,
Xiaohui Huang,
Kenneth D. Westover,
Zhaohui Zhang,
Bin Chen,
Yunpeng Hua,
Shaoqiang Li,
Ruiyun Xu,
Nan Lin,
Baogang Peng,
Shunli Shen
Affiliations
Hong Peng
Department of General Surgery, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China
Yi Zhang
Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China; Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat- sen University, Guangzhou 510630, PR China
Zhiwei Zhou
Department of Radiation Oncology and Biochemistry, University of Texas Southwestern Medical Center at Dallas, TX 75235, USA
Yu Guo
Department of General Surgery, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China
Xiaohui Huang
Department of General Surgical Laboratory, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China
Kenneth D. Westover
Department of Radiation Oncology and Biochemistry, University of Texas Southwestern Medical Center at Dallas, TX 75235, USA
Zhaohui Zhang
Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China
Bin Chen
Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China
Yunpeng Hua
Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China
Shaoqiang Li
Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China
Ruiyun Xu
Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat- sen University, Guangzhou 510630, PR China
Nan Lin
Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat- sen University, Guangzhou 510630, PR China
Baogang Peng
Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China; Corresponding authors at: Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China.
Shunli Shen
Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, PR China; Corresponding authors at: Department of Hepatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China.
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 associated 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. Fund: National Natural Science Foundation of China; Natural Science Foundation of Guangdong Province; Young Teacher Training Program of Sun Yat-sen University; Science and Technology Plan of Guangdong Province; Special Support Program of Guangdong Province, Science and Technology Innovation Youth Talent Support Program; the Pearl River Science and Technology New Talent of Guangzhou City; Medical Scientific Research Foundation of Guangdong Province. Keywords: ELMO1, Tumour mutation burden, Epithelial-mesenchymal transition, Hepatocellular carcinoma
