Comprehensive Analysis of the E2F Transcription Factor Family in Human Lung Adenocarcinoma

Abstract

Qixun Wang,1,* Jinping Liu,1,* Iokfai Cheang,2,* Jinghang Li,3 Tingzhen Chen,4 Yanxiu Li,4 Bo Yu1 1Department of Cardiovascular Surgery, The First People’s Hospital of Lianyungang, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, 222000, Jiangsu, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China; 3Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China; 4Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo Yu, Department of Cardiovascular Surgery, The First People’s Hospital of Lianyungang, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, 222000, Jiangsu, People’s Republic of China, Email [email protected] Yanxiu Li, Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of China, Email [email protected]: E2F transcription factors (E2Fs), code a family of pivotal transcription factors, have been identified as key regulators in tumor tumorigenesis. However, the function of E2F family in human lung adenocarcinoma (LUAD) have not been fully elucidated.Methods: Herein, The Cancer Genome Atlas (TCGA) databases, Kaplan-Meier plotter, cBioPortal and TIMER were used to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of E2Fs in LUAD patients.Results: The expression levels of E2Fs (E2F1-8) were all significantly upregulated in LUAD tissues compared with normal lung tissues. All eight E2Fs had low rates of gene mutation in LUAD patients from cBioPortal databases. Survival analysis revealed that E2F2 (P=0.038; HR 1.36; 95% CI 1.02– 1.81), E2F7 (P< 0.001; HR 1.78; 95% CI 1.33– 2.39) and E2F8 (P=0.03; HR 1.37; 95% CI 1.02– 1.82) were significantly associated with poor prognosis. Multivariate cox regression analysis found that only E2F7 (P< 0.001; HR 2.72; 95% CI 1.75– 4.25) was an independent prognostic predictor in LUAD after adjusting common clinical parameters. The receiver operating characteristic (ROC) analysis also found that E2F7 had high diagnostic value for LUAD (AUC=0.901). Further analysis found that E2F7 was significantly associated with LUAD immune cell infiltration of B cell, T cell, neutrophil, and myeloid dendritic cell. E2F7 also have positive correlations with immune checkpoint genes including SIGLEC15, CD274, HAVCR2, PDCD1LG2, CTLA4, TIGIT, LAG3 and PDCD1 in LUAD.Conclusion: Our findings showed various association of E2F7 in LUAD diagnostic and prognostic aspects, which suggested its potential in becoming a novel biomarker.Keywords: lung adenocarcinoma, E2F transcription factors, TCGA, prognosis, immune cell infiltration

Keywords

• lung adenocarcinoma
• e2f transcription factors
• tcga
• prognosis
• immune cell infiltration.