Increased expression and immune cell infiltration of E2F1/2 collerate with better prognosis in thyroid cancer

Abstract

Abstract Purpose: This study aimed to explore the expression of E2Fs gene family in thyroid cancer(THCA) patients, and systematically analyze the relationship between E2Fs gene and immune cell infiltration and prognosis of THCA patients. Methods: We utilized the UALCAN, cBioPortal, Kaplan-Meier Plotter, Human Protein Atlas, GEPIA, Metascape, Linkedomics and TIMER online databases to explore the transcription level, protein level, genetic alteration and the biological functions of E2Fs, and its relationship with the prognosis and infiltration of immune cell in thyroid cancer patients. Results: ① The expressions of E2F1/7 were significantly increased in the tumor group, while the expressions of E2F4/5 were greatly decreased. ②The mutation rate of E2Fs was 32.93% in patients with THCA, and the mutation of E2Fs was significantly associated with shorter disease-specific survival (P=0.0187) and progression-free survival (P=0.0147). ③Higher expression in transcription and protein levels of E2F1 (HR=0.15, 95%CI: 0.05-0.47, P=0.00015) and E2F2 (HR=37, 95%CI: 0.14-1.00, P= 0.041) were significantly associated with longer overall survival of THCA patients. ④The expression level of E2F1 was positively correlated with infiltration of B cells (Cor = 0.156, p =5.69e-4) and CD8+ T cells (Cor = 0.096, p = 3.35e-2). The expression level of E2F2 was positively correlated with infiltration of B cells (Cor = 0.433, p =2.01e-2), CD8+ T cells (Cor = 0.296, p =2.55e-11), CD4+ T cells (Cor = 0.213, p =1.97e-6), Macrophages (Cor = 0.277, p =4.94e-10), neutrophils (Cor = 0.362, p =1.35e-16) and dendritic cells (Cor = 0.479, p =3.98e-29). Conclusions: E2F1/2 were potential the prognostic markers of THCA patients. Their functions may be related to cell cycle and DNA replication signaling pathways, and promoting multiple immune cell infiltration.