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

Abstract

Background 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.

Prognostic role of E2F1 gene expression in human cancer: a meta-analysis

“…In fact, previous studies have found that E2F1 expression was elevated in tumor tissues and associated with the poor prognosis of cancer. The expression levels of E2Fs (E2F1-8) were all significantly up-regulated in LUAD tissues [ 14 ], Wang et al investigated the expression, prognosis value, mutation, and potential relationship with immunological aspects of E2Fs in LUAD by bio-informatics analysis [ 14 ].E2F1 is expressed strongly in 59.8% of ESCC and that the over-expression was correlated with tumor progression, lymph node metastasis, and poor prognosis after surgery [ 16 ]. Over-expression of E2F1 was significantly associated to worsen OS in all NSCLC patients followed for 200 months, as well as in LUAD patients [ 26 ],which was duplicated in HCC patients [ 27 ].…”

“…During article searching, two essays [ 14 , 15 ] regarding to lung adenocarcinoma (LAUD) and lung squamous cell carcinoma (LUSC) were from the same database as an included article [ 15 ] on lung cancer (LC). In order to prevent repeated inclusion of data, we have deleted the above two essays.…”

Prognosis Role of E2F1 in Cancer: a Meta-analysis

“…In fact, previous studies have found that E2F1 expression was elevated in tumor tissues and associated with the poor prognosis of cancer. The expression levels of E2Fs (E2F1-8) were all signi cantly upregulated in LUAD tissues [13], Wang et al investigated the expression, prognosis value, mutation, and potential relationship with immunological aspects of E2Fs in LUAD by bio-informatics analysis [13].E2F1 is expressed strongly in 59.8% of ESCC and that the over-expression was correlated with tumor progression, lymph node metastasis, and poor prognosis after surgery [15]. Over-expression of E2F1 was signi cantly associated to worsen OS in all NSCLC patients followed for 200 months, as well as in LUAD patients [24],which was duplicated in HCC patients [25].…”

“…During article searching, two literatures [13,14] regarding to lung adenocarcinoma (LAUD) and lung squamous cell carcinoma (LUSC) were from the same database as an included article [14] on lung cancer (LC). In order to prevent repeated inclusion of data, we have deleted the above two literatures.…”

IL5RA as an immunogenic cell death-related predictor in progression and therapeutic response of multiple myeloma

“…ICD-related genes ENTPD1, NT5E, CALR, HMGB1, HSP90AA1, ATG5, BAX, CASP8, PDIA3, EIF2AK3, PIK3CA, CXCR3, IFNA1, IFNB1, IL10, IL6, TNF, CASP1, IL1R1, IL1B, NLRP3, P2RX7, LY96, MYD88, TLR4, CD4, CD8A, CD8B, FOXP3, IFNG, IFNGR1, IL17A, IL17RA, and PRF1 summarized by Abhishek et al 20 . Common immune checkpoints include CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, SIGLEC15, and TIGIT 21 . The R software package ggplot2 (v3.3.3) was used to plot scatter plots, correlation heat maps, lollipop diagrams, and calculate correlation coefficients.…”