Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinoma

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalEBioMedicine
DOIs
StatePublished - Jan 1 2019

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Epithelial-Mesenchymal Transition
Tumor Burden
Tumors
Hepatocellular Carcinoma
Mutation
Biomarkers
Natural sciences
Natural Science Disciplines
Aptitude
Technology
Cell growth
Microarrays
Phosphatidylinositol 3-Kinases
Sun
Tumor Microenvironment
Kaplan-Meier Estimate
Solar System
Microarray Analysis
Genes
Innovation

Keywords

  • ELMO1
  • Epithelial-mesenchymal transition
  • Hepatocellular carcinoma
  • Tumour mutation burden

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinoma. / Peng, Hong; Zhang, Yi; Zhou, Zhiwei; Guo, Yu; Huang, Xiaohui; Westover, Kenneth D; Zhang, Zhaohui; Chen, Bin; Hua, Yunpeng; Li, Shaoqiang; Xu, Ruiyun; Lin, Nan; Peng, Baogang; Shen, Shunli.

In: EBioMedicine, 01.01.2019.

Research output: Contribution to journalArticle

Peng, Hong ; Zhang, Yi ; Zhou, Zhiwei ; Guo, Yu ; Huang, Xiaohui ; Westover, Kenneth D ; Zhang, Zhaohui ; Chen, Bin ; Hua, Yunpeng ; Li, Shaoqiang ; Xu, Ruiyun ; Lin, Nan ; Peng, Baogang ; Shen, Shunli. / Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinoma. In: EBioMedicine. 2019.
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AU - Peng, Hong

AU - Zhang, Yi

AU - Zhou, Zhiwei

AU - Guo, Yu

AU - Huang, Xiaohui

AU - Westover, Kenneth D

AU - Zhang, Zhaohui

AU - Chen, Bin

AU - Hua, Yunpeng

AU - Li, Shaoqiang

AU - Xu, Ruiyun

AU - Lin, Nan

AU - Peng, Baogang

AU - Shen, Shunli

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AB - 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.

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