Distinct landscapes of genetic and epigenetic alterations of E2F familygenes between esophageal squamous cell carcinoma and esophageal adenocarcinoma

Abstract Background/Aims: Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are primarily driven by different genetic changes. The E2F transcription factors (E2Fs) are involved in various malignancies; yet little is known about their roles in ESCC and EAC. This study aimed to investigate genetic and epigenetic alterations of the E2F family genes in ESCC and EAC, and to examine whether the differential changes are associated with the distinct mechanisms. Materials and Methods: mRNA and methylation levels of E2F family genes in ESCC and EAC were retrieved from the database UALCAN. The cBioPortal for Cancer Genomics and Search Tool for the Retrieval of Interacting Genes (STRING) database were used to analyze genetic mutations and interaction networks for E2Fs, respectively.Results: The genetic alteration patterns of E2Fs were different between ESCC and EAC. Furthermore, differences in methylation levels, CNV, and mutation frequency in certain E2F family genes were observed between ESCC and EAC. Moreover, E2Fs were co-expressed and interacted with proteins involved in the N6-methyladenosine (m6A) and histone modifications in EC. Additionally, Kaplan–Meier analysis revealed significant lower E2F1, E2F3, E2F5, E2F7, and E2F8 mRNA levels in association with better prognosis for EAC; while lower E2F1, E2F3, E2F6, E2F7, and E2F8 mRNA levels indicated poorer outcome for ESCC. Conclusions: The different patterns of genetic and epigenetic alterations in the E2F family genes between ESCC and EAC are likely to be associated with different mechanisms. Certain E2Fs hold promise as biomarkers for differential diagnosis of EAC and ESCC, and for prognostic prediction.