Elevated E2F6 Expression in Colorectal Cancer Tissues and Its Association With Clinicopathological Features

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Colorectal cancer (CRC) is a leading global malignancy.
• The specific role of E2F transcription factor 6 (E2F6) in CRC pathogenesis is not well-defined.
• Previous studies on E2F6 in CRC have yielded controversial findings.

Purpose of the Study:

• To comprehensively investigate the expression patterns and functional significance of E2F6 in colorectal cancer.
• To evaluate E2F6 as a potential diagnostic biomarker and therapeutic target for CRC.

Main Methods:

• Analysis of E2F6 mRNA expression across 19 platforms, encompassing 2,449 CRC patients and 1,328 controls.
• Evaluation of E2F6 expression using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics.
• Assessment of E2F6 dependency via CRISPR knockout in 52 CRC cell lines and protein validation by immunohistochemistry (IHC) in 200 paired tissues.

Main Results:

• E2F6 was significantly upregulated in CRC tissues compared to controls (sROC AUC = 0.93).
• E2F6 knockout inhibited proliferation in CRC cell lines, and IHC confirmed elevated E2F6 protein levels (AUC = 0.91).
• Higher E2F6 expression correlated with adverse clinicopathological features, including female sex, age ≥ 60 years, advanced T stage, high-grade tumor budding, and higher histological grade.

Conclusions:

• E2F6 is demonstrably overexpressed in colorectal cancer.
• Elevated E2F6 levels are associated with unfavorable clinicopathological characteristics.
• E2F6 shows promise as a diagnostic biomarker and a potential therapeutic target for CRC management and treatment development.