单位：[1]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China[2]Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China[3]National Center for Respiratory Medicine, Beijing 100029, China[4]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China[5]National Clinical Research Center for Respiratory Diseases, Beijing 100029, China[6]Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110001, China中国医科大学附属盛京医院[7]Department of Pathology, Shenyang KingMed Center for Clinical Laboratory Co,.Ltd,Shenyang 110001, China[8]Department of Pulmonary and Critical Care Medicine, First Hospital of China Medical University, Shenyang 110001, China[9]Department of Pulmonary and Critical Care Medicine, Fourth Hospital of China Medical University, Shenyang 110001, China
Background Ephrin receptors (Eph) and their ligands, called ephrins, function in various disease processes. However, the expression level and prognostic value of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear. Methods The Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. Kaplan-Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Immunohistochemistry was used to analyze the expression level and clinical value of ephrin-A3 protein in clinical LUAD tissue. Weighted coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3. CCK-8 assays and colony-forming experiments were used to investigate whether EFNA3 can regulate cell proliferation ability in LUAD. Analysis of lactate, ATP, and glucose uptake levels was used to explore the effect of EFNA3 on glycolysis ability. In addition, we investigated the relationship between EFNA3 and tumor infiltrating immune cells (TIICs). Finally, the potential immunotherapy response prediction value of EFNA3 was also explored. Results In this study, we found that EFNA3 expression was significantly correlated with both overall survival (OS) and progression-free survival (PFS) in LUAD patients based on a comprehensive analysis of the Eph/Ephrin family. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated an independent prognostic risk factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. In vitro experiments confirmed the role of EFNA3 in promoting LUAD cells and showed that it could regulate glycolytic capacity. Moreover, EFNA3 was negatively associated with immunity, stromal infiltration, and several TIICs. Finally, EFNA3 was found to be positively related to multiple immunotherapy biomarkers. Conclusions In conclusion, increased EFNA3 in LUAD patients predicted worse clinical prognosis, promoted LUAD cell proliferation and glycolysis ability, and was related to immunotherapy response.
基金：
Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2020-PT320-001]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81900040]; Liaoning Education Ministry Supporting Foundation [QN2019014]; Liaoning Science and Technology Ministry Supporting Foundation
第一作者单位：[1]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China[2]Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China[3]National Center for Respiratory Medicine, Beijing 100029, China[4]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China[5]National Clinical Research Center for Respiratory Diseases, Beijing 100029, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China[2]Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China[3]National Center for Respiratory Medicine, Beijing 100029, China[4]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China[5]National Clinical Research Center for Respiratory Diseases, Beijing 100029, China
推荐引用方式(GB/T 7714)：
Deng Mingming,Tong Run,Zhang Zhe,et al.EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma[J].CANCER CELL INTERNATIONAL.2021,21(1):doi:10.1186/s12935-021-02226-x.
APA：
Deng, Mingming,Tong, Run,Zhang, Zhe,Wang, Tao,Liang, Chaonan...&Hou, Gang.(2021).EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma.CANCER CELL INTERNATIONAL,21,(1)
MLA：
Deng, Mingming,et al."EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma".CANCER CELL INTERNATIONAL 21..1(2021)
