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

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.

Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease: an exploratory study

“…ELMO1 encodes a member of the engulfment and cell motility protein family and has been previously linked to T2DM [ 84 – 86 ], hepatocellular carcinoma [ 87 ] and inflammatory arthritis [ 88 ]. Previous methylation analyses of this gene have shown associations with gastric cancer [ 89 ] and CKD [ 20 ].…”

Cell adhesion in cancer: Beyond the migration of single cells

“…This process in normal physiological conditions contributes to embryogenesis, organ development, and wound healing, whereas in cancer, it supports several malignant traits, including metastatic spread and drug resistance (48). In tumors, the EMT phenotype was also reported to be associated with a more inflammatory tumor microenvironment and was thus proposed as a potential biomarker for immune checkpoint blockade agents (49,50). However, the impact of epithelial-mesenchymal transition in the efficiency of this blockade is still unknown.…”

Exploration of the role of tumor mutation burden in clinical significance, immunotherapy response predictor and immune cell infiltration in colon cancer

“…The change in immune microenvironment could affect immunotherapy response and have an impact of prognosis in patients with different cancers [25][26][27][28] . Based on these, TMB is becoming a hot biomarker for various cancers [29][30][31][32][33][34][35][36] . However, the role of TMB in colon cancer is still unde ned 14,34,36,37 .…”