Intergrated Analysis of ELMO1, Serves As a Link between Tumor Mutation Burden and Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

Epithelial-mesenchymal transition (EMT) is critical for cancer cell metastasis. Recently, EMT was reported to be associated with inflammatory tumor microenvironment and therefore might be a predictive biomarker for immune checkpoint blockade agents. However, nderlying mechanism is still unclear. Here, we report an indispensable role for ELMO1 in linking EMT with tumor mutation burden (TMB), which is a promising biomarker for immune checkpoint blockade agent response. Upregulated ELMO1 expression is associated with 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 signaling. Moreover, ELMO1 is negatively associated with TMB, indicating a negative relationship between EMT and TMB. These findings provide mechanistic basis for further development of ELMO1 as a therapeutic target against HCC and might be a promising biomarker of immune checkpoint blockade agent response. Funding: This work was supported by National Natural Science Foundation of China (81302142, 81172039, 81671805, 81602723), Natural Science Foundation of Guangdong Province (S2011010005864; 2014A030313108, 2018A030313529), Young Teacher Training Program of Sun Yat-sen University (15ykpy15), Science and Technology Plan of Guangdong Province (2013B021800134, 2017A020215125), Special Support Program of Guangdong Province, Science and technology innovation youth talent support program (No. 201627015), the Pearl River Science and Technology New Talent of Guangzhou City (No. 201806010076), and Medical Scientific Research Foundation of Guangdong Province (A2015313). Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: consent was obtained for each enrolled patient, and the research was carried out with approval from the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University (Guangdong, China).