3039 - Kat5 as a Prognostic Biomarker and Therapeutic Target in Esophageal Squamous Cell Carcinoma

Purpose/Objective(s): This study investigates the correlation between lysine acetyltransferase 5 (Kat5) expression and the prognosis of esophageal squamous cell carcinoma (ESCC).

Materials/Methods: Tumor tissues from 124 ESCC patients underwent immunohistochemical staining to evaluate Kat5 expression and its prognostic significance. Functional studies included colony formation assays to assess radiosensitivity and cell proliferation after KAT5 knockdown in esophageal cancer cell lines, along with invasion assays using the Transwell system. In vivo experiments included tumorigenesis studies in nude mice to evaluate tumor growth, and small-animal imaging to track metastasis following tail vein injection of tumor cells. Global m6A levels were measured using a quantification kit, while the expression of key m6A modification enzymes was evaluated by WB and qRT-PCR.

Results: Immunohistochemical analysis categorized ESCC patients into three groups based on Kat5 expression levels: low, moderate, and high. Patients with high Kat5 expression had significantly poorer prognoses compared to those with lower levels. In vitro, Kat5 knockdown reduced cell proliferation, invasion, and enhanced radiosensitivity. Tumor growth was notably slower in mice injected with low-Kat5-expressing cells, and pulmonary metastases were absent in the low-Kat5 group but evident in controls. Mechanistically, Kat5 knockdown reduced global m6A levels and suppressed the expression of the m6A methyltransferase METTL16.

Conclusion: High Kat5 expression predicts poor prognosis in ESCC patients, highlighting its potential as a therapeutic target.